The Role of Circulating MicroRNAs as Biomarkers and Therapeutic Targets in Venous Thromboembolism: A Systematic Review.

1. Introduction

Venous thromboembolism (VTE), encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE), is a major cardiovascular disorder and a leading cause of vascular mortality [ 1 ]. Its incidence is 1–2 per 1000 person-years, with a lifetime risk of approximately 8%, affecting over 1.2 million individuals annually in the United States and approximately 10 million worldwide [ 2 , 3 , 4 , 5 , 6 ]. Recent nationwide data from China demonstrated an increasing incidence and serious mortality burden of VTE, challenging the traditional perception that VTE is markedly less common in Asian populations than in Western countries [ 7 ]. PE is the most severe presentation, accounting for the majority of VTE-related deaths and an approximately 20% one-year mortality rate [ 8 , 9 ]. VTE also confers substantial long-term morbidity: approximately 30% of patients experience recurrence within 10 years, and complications including post-thrombotic syndrome (PTS), post-pulmonary embolism syndrome, anticoagulant-related bleeding, and chronic thromboembolic pulmonary hypertension (CTEPH) impair quality of life and increase healthcare utilization [ 10 , 11 , 12 , 13 , 14 , 15 ]. The annual economic burden reaches €1.5–3.3 billion in Europe and US$7–10 billion in the United States [ 16 , 17 ].

Biomarkers have an established but complementary role in the diagnosis and risk stratification of VTE. D-dimer is the principal circulating biomarker used in the diagnostic evaluation of suspected VTE and, because of its high sensitivity, is particularly useful for excluding VTE in patients with a low or intermediate clinical probability. However, its specificity is limited because D-dimer concentrations may also be elevated with increasing age and in numerous conditions, including cancer, infection, inflammation, pregnancy, trauma, and recent surgery. In patients with acute PE, cardiac troponins and natriuretic peptides, particularly B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide, are well-established additional biomarkers for assessing myocardial injury and right ventricular strain and are primarily used for prognostic risk stratification rather than diagnosis [ 18 , 19 , 20 ]. Other circulating markers reflecting inflammation, endothelial activation, myocardial stress, coagulation, and fibrinolysis have also been investigated, including C-reactive protein, heart-type fatty acid-binding protein, soluble P-selectin, von Willebrand factor, and several coagulation and fibrinolytic mediators. However, none has replaced D-dimer in routine VTE diagnostic algorithms or provided sufficient specificity and reproducibility for broad clinical application [ 18 , 19 , 20 ].

These limitations have stimulated the search for biomarkers that may more specifically reflect the biological processes underlying VTE and potentially provide information beyond the presence of fibrin formation and degradation. Circulating microRNAs (miRNAs) have emerged as promising epigenetic biomarker candidates because they are detectable in blood, exhibit relative stability in the circulation, and can be quantified using sensitive molecular techniques. Their stability is enhanced by their association with extracellular vesicles, lipoproteins, and RNA-binding proteins, which protect them from degradation. In contrast to conventional protein biomarkers that often represent downstream consequences of thrombosis, altered miRNA expression may reflect upstream and interconnected biological processes involved in thrombogenesis, including endothelial dysfunction, platelet activation, inflammation, coagulation, and fibrinolysis. Furthermore, individual miRNAs or miRNA signatures may provide disease-related molecular information and potentially improve diagnostic, prognostic, or phenotypic characterization when used in combination with established clinical and laboratory approaches. These potential advantages have prompted increasing investigation of circulating miRNAs as biomarkers of VTE, although their clinical utility remains to be established through standardized assays and prospective external validation.

miRNAs are small endogenous noncoding RNAs (19–24 nucleotides) that regulate gene expression post-transcriptionally by binding to the 3′ untranslated region of target messenger RNAs (mRNAs), thereby inducing mRNA degradation or translational repression [ 21 ]. A single miRNA may regulate multiple genes, collectively influencing a large proportion of the human transcriptome (approximately 90%) and controlling processes including cell-cycle regulation, apoptosis, proliferation, and differentiation [ 22 ]. miRNAs are key regulators in numerous diseases [ 23 , 24 ] and can be detected in body fluids by Northern blotting, quantitative real-time polymerase chain reaction (qRT-PCR), microarray analysis, and next-generation sequencing [ 25 ]. Aberrant miRNA expression has been linked to cardiovascular, neoplastic, and autoimmune conditions [ 26 , 27 ]. In hemostasis, miRNAs modulate endothelial cells, platelets, and leukocytes and regulate procoagulants, including fibrinogen, factor XI, and tissue factor (TF); anticoagulants, including tissue factor pathway inhibitor, antithrombin, and protein S; and fibrinolytic mediators, including plasminogen activator inhibitor-1 (PAI-1) [ 28 , 29 , 30 ]. Given these broad regulatory roles, miRNA dysregulation may contribute to VTE pathogenesis while also providing measurable signatures of the underlying thrombotic processes.

Despite the rapid growth of this field, systematic syntheses of the available evidence remain limited. This systematic review aimed to comprehensively evaluate the current evidence regarding miRNAs in VTE, with particular emphasis on their mechanistic roles, circulating biomarker potential, and possible therapeutic relevance, while distinguishing promising translational candidates from findings that remain predominantly preclinical.

2. Materials and Methods

Eligibility criteria were defined a priori according to Population, Intervention/Exposure, Comparator, Outcomes, and Study design. Inclusion criteria were: (i) Population—laboratory systems (cell lines, primary cells, tissues, and animal models) or human participants comprising patients with VTE, healthy controls, or individuals at increased risk of VTE; (ii) Intervention/exposure—evaluation of miRNA function, expression, or diagnostic/prognostic value; (iii) Comparator—baseline versus miRNA mimic/inhibitor conditions (laboratory studies) or VTE versus non-VTE/healthy participants (clinical studies); (iv) Outcomes—cellular or molecular miRNA effects or diagnostic, prognostic, or therapeutic endpoints; (v) Study designs—in vitro, in vivo, and ex vivo experiments and cohort, case–control, or cross-sectional studies; and (vi) English-language, peer-reviewed original research. Exclusion criteria were: (i) conference abstracts, case reports, editorials, letters, narrative and systematic reviews, and meta-analyses; (ii) retracted publications; and (iii) studies focused primarily on VTE complications (PTS, CTEPH, post–pulmonary embolism syndrome) or on VTE in uncommon anatomical locations. All studies that met the predefined inclusion criteria and did not meet any exclusion criteria were included in the systematic review.

A comprehensive literature search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [ 31 ] ( Figure 1 ). PubMed and EMBASE were queried up to 15 December 2025, using the following keywords: “miR” OR “miRNA” OR “microRNA” combined with “venous thromboembolism,” “deep vein thrombosis,” “pulmonary embolism,” “lung thrombosis,” and “lung embolism.” Reference lists of prior reviews were also screened manually. This process did not identify any additional eligible publications. PubMed and EMBASE were selected as the primary information sources because, in combination, they provide comprehensive indexing of the biomedical and pharmacological literature pertinent to miRNAs in venous thromboembolism. Two independent reviewers screened titles and abstracts, with disagreements resolved by a third reviewer. Extracted data included authors, publication year, investigated miRNAs, study design, functional role, expression patterns, mechanisms of action, identified targets, and diagnostic potential. Given the methodological heterogeneity of the studies included, a narrative synthesis was undertaken, and no meta-analysis, pooled statistical analysis, or other inferential statistical methods were performed. The review was not prospectively registered, and no formal review protocol was published. The completed PRISMA 2020 checklist is provided as Supplementary Table S1 .

The risk of bias of the included studies was assessed according to study design using three established tools. The assessments were independently performed by two reviewers, with disagreements resolved through discussion and, when necessary, adjudication by a third reviewer. In vitro studies were evaluated using the Quality Assessment Tool for In Vitro Studies (QUIN), which assesses potential sources of bias related to study objectives, sample-size justification, sample preparation, allocation and randomization, blinding, outcome assessment, statistical analysis, and reporting. Animal studies were assessed using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk-of-bias tool, which evaluates selection, performance, detection, attrition, reporting, and other potential sources of bias. Clinical observational studies were assessed using the Newcastle–Ottawa Scale (NOS), with the appropriate case–control or cohort version applied according to the design of each study. Because the three tools use different domains and scoring approaches, the risk-of-bias findings for in vitro, animal, and clinical studies are separately presented in Supplementary Table S2, Supplementary Table S3 and Supplementary Table S4 , respectively. An overall summary of the included studies, including their key characteristics and study designs, is provided in Supplementary Table S5 .

For data synthesis, miRNAs were classified as prothrombotic or antithrombotic according to the predominant net effect on thrombus formation, progression, resolution, or overall thrombus burden reported in each source study, rather than solely based on a single direct molecular mechanism. When a miRNA demonstrated pleiotropic, context-dependent, or opposing effects across experimental models, study populations, or venous thromboembolism entities, its classification was based on the predominant direction of the reported evidence. miRNAs for which the available findings did not support a consistent net prothrombotic or antithrombotic effect were categorized as unclassified. Gene symbols are italicized throughout the manuscript; the corresponding encoded proteins, or the non-protein-coding RNA products where applicable, are summarized in the Gene Nomenclature table.

3. Results

A total of 914 records were identified through database searching. After removing 209 duplicate records, 705 records remained for screening. Of these, 363 records were excluded based on the predefined exclusion criteria. The remaining 342 records were assessed for eligibility, and 186 were excluded because they did not meet the inclusion criteria. Ultimately, 156 studies were included in the systematic review.

Among the 156 studies included in the systematic review, 106 (67.9%) contained an in vitro component, 67 (42.9%) incorporated an animal (in vivo) model, and 98 (62.8%) included a human clinical study with a case–control or cohort design. Because these categories were not mutually exclusive, several publications combined two or more study-design components, reflecting the heterogeneous and translational nature of the available evidence, ranging from mechanistic laboratory investigations to preclinical models and clinical observations ( Supplementary Table S5 ).

3.1. Deep Venous Thrombosis

We identified 99 studies investigating the role of miRNAs in the DVT setting. DVT-associated miRNAs were classified as pro-thrombotic, anti-thrombotic, or unclassified miRNAs. Detailed overviews are presented in Table 1 and Table 2 .

3.2. Pro-Thrombotic miRNAs in Deep Venous Thrombosis

Thirty studies reported miRNAs with pro-thrombotic properties in the DVT setting. These miRNAs are listed in Table 1 .

Elevated miR-92a-3p levels were reported to promote angiogenesis through a TUG1 /miR-92a-3p/ Hmgcr axis in DVT; TUG1 overexpression or miR-92a-3p inhibition reduced thrombosis in vivo [ 32 ]. miR-93-5p was shown to regulate endothelial and macrophage functions in DVT. Knockdown of the long noncoding RNA (lncRNA) NORAD enhanced human umbilical vein endothelial cell (HUVEC) proliferation and reduced apoptosis and inflammation, whereas miR-93-5p overexpression reversed these effects. In addition, NORAD discriminated DVT from controls (AUC 0.919) and predicted PTS [ 33 ]. A second study showed that lncRNF219-3:1 sponges miR-93-5p to upregulate T-cell immunoglobulin and mucin domain-containing protein 4, thereby suppressing nuclear factor kappa B (NF-κB)-mediated inflammation [ 34 ]. miR-96 was shown to suppress VAMP8 and reduce platelet activation. Postoperative platelet miR-96 levels correlated with D-dimer levels in orthopedic patients with DVT [ 35 ].

miR-125a-5p was reported to be upregulated in patients with DVT, and its levels showed a high diagnostic performance (AUC >0.8 alone; >0.97 combined with D-dimer) for DVT diagnosis. It inhibited endothelial progenitor cell (EPC) migration and angiogenesis through the MCL1 apoptosis regulator protein and phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling by targeting ANGPT2 [ 36 , 37 , 38 ]. miR-128-3p was also upregulated in patients with DVT and promoted endothelial injury by targeting SIRT1 [ 39 ]. Resveratrol-mediated suppression of miR-138 facilitated EPC-mediated DVT recanalization through upregulation of focal adhesion kinase [ 40 ]. The CASC2 /miR-152-3p axis showed high diagnostic performance in a study of 150 patients with DVT and controls; miR-152-3p was reported to target genes involved in transforming growth factor beta and PI3K/Akt signaling [ 41 ].

miR-195 was evaluated in four studies and was consistently elevated in patients with DVT. Reported diagnostic performance was very high, with AUC values of up to 1.000. Mechanistic studies identified GABARAPL1 , NOS3 , and BCL2 as targets involved in endothelial function and cell-survival pathways [ 42 , 43 , 44 , 45 ]. miR-197-3p was reported to reduce CXCR2 levels, with downstream upregulation of cyclooxygenase-2 and activation of NF-κB, resulting in reduced endothelial-cell viability and angiogenesis and increased inflammatory cytokine release in DVT patients [ 46 ]. miR-199b-5p was increased in patients with DVT after total knee arthroplasty, and the combination of miR-199b-5p and nitric oxide achieved an AUC of 0.847 for DVT diagnosis [ 47 ].

miR-206 overexpression inhibited EPC function through GJA1 upregulation and aggravated thrombosis in mouse models [ 48 ]. miR-320 levels were elevated in patients with DVT (fold change 1.58–1.79; AUC 0.70–0.79) and correlated with D-dimer levels. Administration of a miR-320a antagonist reduced thrombus size and prolonged clotting time in a rat DVT model [ 49 , 50 , 51 ]. miR-374a-5p was elevated in patients with DVT after total hip arthroplasty (AUC up to 0.974). Administration of a miR-374b-5p agonist aggravated DVT formation by decreasing interleukin-10 expression in a mouse model [ 52 , 53 ].

miR-383-5p overexpression increased endothelial-cell apoptosis through the MALAT1 /miR-383-5p/ BCL2L11 axis [ 54 ]. miR-424-5p was evaluated in two DVT studies and was upregulated in patients with DVT, with modest diagnostic performance (AUC 0.630). miR-424-5p was reported to suppress SNHG12 expression, a change associated with endothelial-cell activation and the release of inflammatory cytokines and adhesion factors, primarily through PI3K/Akt signaling [ 55 , 56 ]. miR-448 was increased in peripheral blood mononuclear cells (PBMCs) from patients with DVT compared with non-DVT controls and contributed to the inflammatory response through downregulation of SIRT1 [ 57 ].

miR-499 levels decreased following curcumin administration in vitro. miR-499 overexpression inhibited the proangiogenic effects of curcumin on endothelial cells by targeting PTEN [ 58 ]. miR-503-5p was identified as a risk factor for DVT in patients with multiple myeloma (MM) and showed considerable diagnostic performance for DVT prediction (AUC 0.848). miR-503-5p mediated proinflammatory and prothrombotic endothelial responses by targeting WNT3A [ 59 ]. miR-542-3p inhibited angiogenesis by targeting ANGPT2 [ 60 ], whereas miR-6132 upregulation promoted inflammation by targeting FOXP3 , resulting in DVT formation [ 61 ].

3.3. Anti-Thrombotic miRNAs in Deep Venous Thrombosis

Sixty-three studies reported antithrombotic miRNAs in the DVT setting. These miRNAs are listed in Table 2 .

The increased levels of let-7e-5p enhanced EPC migration and tube formation by targeting FASLG , thereby promoting thrombus revascularization in vivo [ 62 ]. miR-9 enhanced EPC migration and angiogenesis through FGF5 regulation and TRPM7 /PI3K/Akt/autophagy signaling [ 63 , 64 ]. miR-21 was evaluated in four studies in the DVT setting. Cancer-derived exosomal miR-21 enhanced EPC function through IL6R targeting [ 65 ]. Reduced miR-21 levels in patients with DVT predicted recurrence and PTS [ 66 ]. Berberine improved EPC function by increasing miR-21-3p levels; miR-21-3p targets RRAGB , which regulates mechanistic target of rapamycin (mTOR) signaling [ 67 ]. The GAS5 /miR-21/ PTEN axis suppressed PI3K/Akt/NF-κB signaling, resulting in DVT improvement [ 68 ].

miR-22-3p was upregulated in EPCs from DVT patients, and its inhibition enhanced EPC proliferation through the OC1/ VEGFA pathway. Lower miR-22-3p levels were associated with a reduced risk of DVT recurrence [ 69 ]. In another study, the hsa_circ_000455/miR-22-3p/ NLRP3 axis was implicated in DVT [ 70 ]. miR-26a was reported to be downregulated in DVT. Its levels correlated inversely with CCL2 and CCL7 and showed moderate diagnostic value for DVT (AUC 0.73) [ 71 , 72 ].

The circular RNA circ_0001020 sponged miR-29c-3p and upregulated MDM2 , thereby impairing EPC function. Knockdown of circ_0001020 reduced thrombosis in a mouse DVT model [ 73 ]. miR-103a-3p was reported to be downregulated in DVT in three studies and targeted CXCL12 , HMGB1 , and PTEN to reduce inflammation and improve EPC function [ 74 , 75 , 76 ]. miR-122 overexpression protected HUVECs from oxidative stress by suppressing p53 [ 77 ].

The LINC01123 /miR-125a-3p/ IL1R1 axis was shown to promote DVT. Within this axis, miR-125a-3p suppression reduced thrombus burden in a rat DVT model [ 78 ]. miR-126 supported EPC function and thrombus resolution by targeting PIK3R2 and FOXO4 across three studies [ 79 , 80 , 81 ]. miR-136-5p was downregulated in DVT, and restoration of its expression reduced thrombus formation and levels of inflammatory mediators, including interleukin-6 (IL-6) and C-reactive protein. EPC-derived extracellular vesicles restored miR-136-5p in a mouse DVT model while suppressing TXNIP as a target [ 82 , 83 ].

A circular RNA–miRNA network study identified a CBT15_circR_28491–miR-139-3p– Kif18a / Cdca8 / Nek2 axis as a potential regulatory pathway in DVT [ 84 ]. miR-143-3p promoted EPC function through ATG2B regulation and contributed to DVT recanalization. LINC00659 and UXT-AS1 were reported to sponge miR-143 in high-altitude DVT and thereby regulate prothrombotic gene expression [ 85 , 86 ]. miR-145 reduced TF expression and thrombogenesis in preclinical DVT models; however, its clinical evaluation in 360 patients with suspected DVT showed low diagnostic performance (AUC 0.59) [ 87 , 88 ]. The circUSP9X/miR-148b-3p/ SRCIN1 axis was implicated in endothelial injury in DVT [ 89 ].

miR-150 was reported to be downregulated in EPCs from patients with DVT. Its overexpression enhanced EPC proliferation, angiogenesis, and thrombus resolution through MYB and SRCIN1 in three studies [ 90 , 91 , 92 ]. The CRNDE /miR-181a-5p/ PCYOX1L axis contributed to thrombus development in a mouse DVT model [ 93 ]. miR-181b was reduced in patients with DVT and showed high diagnostic accuracy (AUC 0.880–0.953 when combined with D-dimer). Its overexpression enhanced HUVEC viability and migration through HEY2 targeting [ 94 , 95 ]. miR-181c-5p overexpression reduced apoptosis, oxidative stress, and thrombosis-related markers in the DVT setting by targeting FOS [ 96 ].

miR-185 overexpression suppressed TF and fibrin formation by modulating PI3K/Akt and mitogen-activated protein kinase (MAPK) signaling [ 97 ]. miR-199a overexpression enhanced EPC-mediated recanalization through TAB2 targeting [ 98 ]. miR-204-5p exerted antithrombotic and anti-inflammatory effects through SPRED1 and P4HB in two DVT studies [ 99 , 100 ]. miR-205 overexpression promoted EPC homing and thrombus recanalization by targeting PTEN [ 101 ]. The NEAT1 /miR-218-5p/ GAB2 axis promoted endothelial apoptosis and inflammation in DVT [ 102 ].

miR-223 was evaluated in four studies. Its upregulation reduced blood viscosity, decreased inflammatory mediators, and enhanced EPC function. These effects were attributed to regulation of TLR2 , MYD88 , c-Jun N-terminal kinase, FOXO1 , and NLRP3 . miR-223 also showed high diagnostic value (AUC >0.8) when combined with miR-125a-5p for DVT diagnosis [ 36 , 103 , 104 , 105 ]. miR-296-5p regulated endothelial function in DVT by promoting endothelial apoptosis, oxidative stress, and endothelial-to-mesenchymal transition. These effects involved MEG8 and S100A4 . Inhibition of miR-296-5p aggravated thrombosis in vivo [ 106 , 107 ].

miR-338-5p directly targeted IL-6, and its overexpression reduced IL-6 levels and attenuated DVT in vivo [ 108 ]. Exosome-delivered miR-342-3p inhibited thrombus formation by targeting EDNRA [ 109 ]. miR-361-5p downregulation accelerated thrombus resolution through FGF1 targeting [ 110 ]. miR-411 overexpression suppressed vein-wall fibrosis in DVT rats through hypoxia-inducible factor-1 alpha-dependent matrix metalloproteinase-2 downregulation [ 111 ].

miR-421 directly targets SERPINE1 mRNA, which encodes PAI-1, thereby influencing fibrinolytic balance [ 112 ]. Elevated plasma miR-423-5p levels outperformed D-dimer for the detection of DVT in elderly patients with fractures (AUC 0.663 versus 0.491) [ 113 ]. Inhibition of miR-483-3p enhanced EPC homing [ 114 ], whereas miR-483-5p-enriched exosomes reduced TF expression and NLRP3 inflammasome activation by targeting MAPK1 [ 115 ].

miR-495 overexpression suppressed the IL1R1 / TLR4 axis and reduced thrombus burden in a rat DVT model [ 116 ]. miR-497-5p promoted EPC function and reduced thrombus formation through LITAF targeting [ 117 ]. miR-513c-5p overexpression reduced caspase-1 levels and attenuated DVT by limiting inflammasome-driven interleukin-1 beta and interleukin-18 production [ 118 ]. miR-525-5p enhanced HUVEC viability and reduced apoptosis through the LINC00659 /miR-525-5p/ BAX axis in the DVT setting [ 119 ].

The role of miR-758-5p in DVT was associated with a single-nucleotide polymorphism (SNP) that altered miR-758-5p binding to BDKRB2 mRNA, resulting in changes in vascular gene regulation [ 120 ]. miR-2467-3p negatively regulated ABLIM1 , and its knockdown improved endothelial-cell function and reduced inflammation in DVT [ 121 ].

miR-3120-5p inhibited the PI3K/Akt/mTOR pathway and matrix metalloproteinase-1 expression, thereby regulating EPC migration and angiogenesis through WTAPP1 [ 122 ]. miR-5189-3p mimics promoted thrombus organization and recanalization through Notch signaling involving JAG1 , NOTCH1 , and HES1 in a rat DVT model [ 123 ].

3.4. Unclassified miRNAs in Deep Venous Thrombosis

In six studies, we were unable to classify the miRNAs according to their reported roles. One study identified eight differentially expressed miRNAs (miR-150-5p, miR-326, miR-144-3p, miR-199a-5p, miR-199b-5p, miR-125a-5p, let-7e-5p, and miR-381-3p) in human DVT, with enrichment of p53, PI3K/Akt, and MAPK pathways and diagnostic value reported for PDE1B and IRS1 [ 124 ]. A stasis-induced rat DVT microarray study identified 19 miRNA regulatory networks enriched in endothelial-cell functional pathways [ 125 ]. A mouse inferior vena cava stasis model identified a competing endogenous RNA (ceRNA) network comprising 20 lncRNAs, 54 miRNAs, and 166 mRNAs, with miR-6396, miR-1946a, and miR-466 family members as key nodes [ 126 ].

In another study, elevated hsa_circ_101209 in pregnancy-related DVT correlated with D-dimer (r = 0.358) and was predicted by Encyclopedia of RNA Interactomes analyses to bind 15 miRNAs. A three-marker panel achieved an AUC of 0.953 for DVT diagnosis [ 127 ]. A multi-omics DVT study identified a hsa_circ_0095124/hsa-miR-3074-5p/ TNFSF13B ceRNA axis and nominated JAK2 , CD36 , TNFSF13B , TLR7 , and PARP9 as hub regulators [ 128 ]. Finally, a study of hip fracture-associated DVT identified a ceRNA network including hsa-miR-93-5p and hsa-miR-320b; the HSF2 –hsa-miR-139-5p mRNA–miRNA interaction was confirmed by qRT-PCR, linking immune signaling to thrombosis [ 129 ].

3.5. Pulmonary Embolism

Twenty-five studies investigated the role of miRNAs in the setting of PE, using cell lines, animal models, and clinical samples. PE-associated miRNAs were categorized as prothrombotic or antithrombotic, with unclassified miRNAs summarized separately. Detailed overviews are presented in Table 3 and Table 4 .

3.6. Prothrombotic miRNAs in Pulmonary Embolism

Fifteen studies reported prothrombotic miRNAs in the PE setting. These miRNAs are listed in Table 3 .

let-7b-5p was upregulated in acute PE and aggravated endoplasmic reticulum stress through SERP1 upregulation [ 130 ]. It also suppressed platelet-derived growth factor-stimulated pulmonary artery smooth muscle cell (PASMC) proliferation by targeting IGF1 [ 131 ]. Plasma miRNA profiling identified let-7i-5p, which was upregulated in acute PE and idiopathic pulmonary arterial hypertension (IPAH), and miR-320a, which was elevated in CTEPH and IPAH. AR and PRKCA were identified as specific targets [ 132 ].

In an experimental rat model of acute PE, miR-21 regulated inflammatory responses and lung injury by targeting PTEN . Curcumin suppressed this axis and reduced mean pulmonary arterial pressure, right ventricular systolic pressure, and thrombus volume [ 133 ]. In another study, berberine suppressed miR-22-5p/ TLR4 /NF-κB signaling in acute PE, thereby reducing PASMC proliferation and pulmonary hypertension [ 134 ].

Both miR-27a and miR-27b were elevated in acute PE and showed enhanced diagnostic accuracy when combined with D-dimer (AUC 0.909) [ 135 ]. miR-28-3p was elevated in a canine PE model (AUC 0.792) [ 136 ] but was reduced in PE endothelial cells, in which its target gene API5 overexpression protected endothelial cells from apoptosis [ 137 ].

Plasma miR-134 was markedly elevated in patients with acute PE and showed strong diagnostic accuracy (AUC 0.833) [ 138 ]. miR-190 and miR-197 were also elevated in patients with PE (AUC 0.78 and 0.79, respectively), and their combination with D-dimer achieved an AUC of 0.954 [ 139 ]. miR-221 was upregulated in patients with acute PE and showed high diagnostic performance (AUC 0.823). Its levels correlated positively with B-type natriuretic peptide, troponin I, and D-dimer [ 140 ]. miR-221-3p promoted PASMC proliferation by targeting PTEN in PE-associated pulmonary hypertension [ 141 ].

miR-514a-5p overexpression exacerbated right ventricular hypertrophy and lung injury in a rat PE model through CHRDL1 downregulation [ 142 ]. miR-1233 showed high diagnostic performance for acute PE versus non-ST-elevation myocardial infarction (AUC 0.95; 90% sensitivity and 100% specificity) [ 143 ]. It also outperformed D-dimer and the Wells score in PE complicating an acute exacerbation of chronic obstructive pulmonary disease (AUC 0.884) [ 144 ].

3.7. Antithrombotic miRNAs in Pulmonary Embolism

Eight studies reported antithrombotic miRNAs in the PE setting. These miRNAs are listed in Table 4 .

miR-22-3p was downregulated in PE-associated cardiac injury. The lncRNA MALAT1 was reported to sponge miR-22-3p and thereby promote NLRP3 -mediated inflammasome injury in PE. Resveratrol restored miR-22-3p levels and attenuated PE-induced NLRP3 activation [ 145 ]. miR-34a-3p was downregulated in acute PE, and restoration of its expression reduced mean pulmonary arterial pressure and pulmonary arterial wall thickening through DUSP1 suppression in PASMCs [ 146 ]. The MEG3 /miR-34a-3p/ DUSP1 axis was subsequently identified as a key regulator of smooth-muscle proliferation and vascular remodeling in PE.

miR-106b-5p downregulation coincided with NOR-1 upregulation in PE models. AgomiR-106b-5p improved survival and attenuated pulmonary vascular proliferation by targeting NOR-1 [ 147 ]. miR-124 regulated endothelial metabolic reprogramming by targeting PTBP1 in a rat PE model [ 148 ]. miR-145 was downregulated in chronic obstructive pulmonary disease-associated PE and correlated positively with the ratio of forced expiratory volume in 1 s to forced vital capacity. Curcumin upregulated miR-145-5p, which targeted IRS1 and reduced myocardial injury [ 149 , 150 ]. miR-150-5p was reduced in acute PE compared with DVT, with a further reduction in PE complicated by pulmonary arterial hypertension (AUC 0.912 for distinguishing PE from DVT) [ 151 ].

3.8. Unclassified miRNAs in Pulmonary Embolism

In two studies, we were unable to classify the miRNAs according to their reported roles.

A six-miRNA panel (miR-363-3p, miR-93-3p, miR-22-5p, miR-451a, miR-222-3p, and miR-140-3p) predicted postsurgical PE in patients with glioma (AUC 0.78) and outperformed the Khorana score [ 152 ].

In a hypoxia-reoxygenation PE model, urokinase restored dysregulated miRNA patterns, including miR-34a-5p, miR-324-5p, miR-331-3p, miR-429, miR-491-5p, and miR-449a. miR-449a overexpression abolished the protective effects of urokinase, identifying it as a mediator of ischemic injury [ 153 ].

3.9. Venous Thromboembolism

Thirty-two studies examined miRNA involvement in the VTE setting. Detailed overviews of prothrombotic and antithrombotic miRNAs in VTE are provided in Table 5 and Table 6 . The unclassified miRNAs were summarized separately.

3.10. Prothrombotic miRNAs in Venous Thromboembolism

Nine studies reported prothrombotic miRNAs in the VTE setting. These miRNAs are listed in Table 5 .

Elevated baseline miR-126 levels correlated with residual thrombosis and may predict persistent thrombotic risk in VTE [ 154 ]. In a bioinformatic analysis enriched for 16 pathways, miR-130a was predicted to have 225 gene targets [ 155 ]. miR-144 levels were increased in VTE and were associated with reduced FOS expression in neutrophils, linking adipokine and inflammatory signaling to VTE pathogenesis [ 156 ].

In hibernating black bears, miR-141-3p, miR-200a-3p, and miR-200c-3p were downregulated and were predicted to target SERPINC1 , which encodes antithrombin, suggesting that reduced expression of these miRNAs may lower thrombotic risk [ 157 ]. miR-200c-3p was upregulated in rat VTE models, and its inhibition reduced thrombus formation. miR-200c-3p levels also correlated inversely with SERPINC1 expression across animal and human samples [ 158 ].

In a glioma case–control study, miR-221-3p and miR-451a were identified as VTE-associated miRNAs, with platelet activity linked to the miRNA profiles [ 159 ]. miR-483-5p levels were increased in VTE and correlated with body mass index and C-reactive protein. miR-483-5p also showed independent predictive value for VTE diagnosis, particularly in patients with lung cancer and a high body mass index [ 160 ].

Plasma miR-3613-5p showed high diagnostic accuracy (AUC 0.805) among multiple upregulated miRNAs in acute VTE and was functionally linked to decreased fibrinogen and increased platelet aggregation [ 161 ]. In another study, six miRNAs (miR-4651, miR-4734, miR-6798-3p, miR-6789-5p, miR-6765-5p, and miR-6816-5p) showed at least fivefold increases in VTE. Pathway analyses implicated thrombomodulin and platelet-related gene regulation as potential targets of these miRNAs [ 162 ].

3.11. Antithrombotic miRNAs in Venous Thromboembolism

Seven studies reported antithrombotic miRNAs in the VTE setting. These miRNAs are listed in Table 6 .

The lncRNA ANRIL promoted angiogenesis and thrombosis by modulating miR-99a and miR-449a in the autophagy pathway in a rat VTE model [ 163 ]. Estradiol-responsive miR-365a-3p targeted the tissue factor 3′ untranslated region and reduced TF-initiated thrombin generation. miR-365a-3p was also downregulated in pregnant women and oral contraceptive users [ 164 ]. miR-200a-5p was downregulated in patients with VTE, and its overexpression enhanced endothelial-cell migration by targeting COX7C [ 165 ].

In patients with cervical cancer, abnormal expression of miR-195-5p, miR-205-5p, and vascular endothelial growth factor A was associated with VTE treatment outcomes [ 166 ]. Circulating miR-522-3p and miR-134 were upregulated in patients with VTE, and combined miRNA and gene-expression profiling supported their diagnostic potential [ 167 ].

In a prospective population-based study (the HUNT study), individuals in the highest miR-145 quartile had a 49% lower risk of VTE (hazard ratio 0.51), with a stronger association for unprovoked VTE, supporting miR-145 as an inverse VTE risk biomarker [ 168 ]. In cervical cancer-related VTE, lower miR-20a-5p levels predicted VTE, whereas lower miR-145-5p levels correlated with improved survival in patients with cervical adenocarcinoma [ 169 ].

3.12. Unclassified miRNAs in Venous Thromboembolism

In sixteen studies, we were unable to classify the miRNAs according to their reported roles.

SNPs in miR-133a2 were associated with warfarin dose variability. GA or AA genotypes required higher weekly doses than wild-type genotypes, supporting a potential role for miR-133a2 polymorphisms in personalized anticoagulation [ 170 ]. Profiling of 97 plasma miRNAs identified distinct signatures that separated patients with VTE from controls, with miR-10b-5p, miR-320a/b, miR-424-5p, and miR-423-5p upregulated and miR-103a-3p, miR-191-5p, miR-301a-3p, and miR-199b-3p downregulated [ 171 ].

In a VTE cohort, 12 miRNAs were significantly associated with recurrence; miR-15b-5p, miR-197-3p, miR-27b-3p, and miR-30c-5p showed time-dependent trends preceding earlier recurrences, and eight miRNAs correlated with transforming growth factor beta 1/2 signaling [ 172 ]. Combined polymorphism analyses in Korean patients with VTE identified three allelic combinations of miR-146a, miR-149, miR-196a2, and miR-499 that were significantly associated with increased VTE risk, supporting polygenic susceptibility [ 173 ].

RAN rs14035 and XPO5 rs11077 polymorphisms were associated with VTE prevalence, and haplotype analysis across DICER1 , DROSHA , RAN , and XPO5 identified protective and risk-conferring variants [ 174 ]. A Bayesian network analysis linked miR-199b-3p to hematocrit and VTE risk; miR-370, miR-27b-3p, and miR-222-3p were associated with recurrence; and 21 novel SNP-miRNA associations were identified in a genome-wide association study [ 175 ].

Four circulating miRNAs (miR-126-3p, miR-885-5p, miR-194-5p, and miR-192-5p) showed significant associations with VTE (odds ratios 1.3–1.8), and a combined risk model including age and sex achieved an AUC of 0.77 [ 176 ]. A seven-miRNA signature predicted future VTE risk (AUC 0.95) and was enriched in complement and coagulation-cascade pathways; adding calprotectin improved risk stratification (AUC 0.77) [ 177 ].

Large-scale sequencing and bioinformatic studies further characterized the miRNA regulatory landscape in VTE: 547 dysregulated miRNAs were identified in one study [ 178 ], and 32 differentially expressed miRNAs implicated hemostatic pathways in another [ 179 ]. A multicohort analysis of 1950 miRNAs identified a weighted miRNA score that predicted VTE outcomes over 8 years and delineated five distinct miRNA networks involving fibrinolytic signaling [ 180 ]. An integrative analysis identified 89 dysregulated miRNAs and CREB1 as a central regulator and validated ESM1 , HIF1A , and CREB1 in unprovoked VTE [ 181 ].

A bioinformatic study of the thrombin-activatable fibrinolysis inhibitor interactome identified 28 hemostasis-related genes targeted by 24 miRNAs that were enriched in complement/coagulation cascades and neutrophil extracellular-trap formation [ 182 ]. A comparative analysis across thrombotic and inflammatory disorders identified 30 shared dysregulated miRNAs linking immunothrombosis and epigenetic regulation [ 183 ].

In coronavirus disease 2019-related VTE, 42 shared differentially expressed genes were identified, with eight hub genes, including COX7C , RSL24D1 , and NDUFA4 , nominated as diagnostic markers within dense transcription-factor–gene and transcription-factor–miRNA co-regulatory networks [ 184 ]. A separate study examined lymphangiogenesis-related VTE mechanisms: MYC , regulated by hsa-miR-449c-5p, and JUN were identified as central hubs, and qRT-PCR confirmed MYC downregulation and NTAN1 upregulation in VTE, linking immune-metabolic dysregulation to thrombotic progression [ 185 ].

4. Discussion

This systematic review synthesized 156 studies on miRNAs in VTE pathogenesis: 99 on DVT, 25 on PE, and 32 on VTE. Several miRNAs were consistently reported across multiple studies, underscoring their potential as biomarkers or therapeutic targets. Among prothrombotic DVT miRNAs, miR-195, miR-125a-5p, miR-320, miR-93-5p, miR-374, and miR-424-5p were validated in both functional and clinical settings. Antithrombotic DVT miRNAs confirmed in multiple studies included miR-21, miR-223, miR-103a-3p, miR-126, miR-150, miR-9, miR-22-3p, miR-26a, miR-136-5p, miR-143, miR-145, miR-181b, miR-204-5p, and miR-296-5p. In PE, prothrombotic miRNAs including let-7b-5p, miR-28-3p, miR-221, and miR-1233 were reproducibly identified, while miR-134 and miR-190/miR-197 showed particularly notable diagnostic performance. Antithrombotic miR-34a-3p and miR-145 were evaluated in multiple PE studies, with miR-145 and miR-150 demonstrating noteworthy cardiopulmonary protective effects.

Across the three VTE categories, no single prothrombotic miRNA was shared among DVT, PE, and VTE simultaneously. let-7b-5p, let-7i-5p, miR-21, and miR-27 were shared between PE and VTE; miR-197-3p and miR-499 were shared between DVT and VTE; and miR-197 and miR-320a were shared between DVT and PE ( Figure 2 ). In contrast, miR-145 was the only antithrombotic miRNA identified across all three categories; miR-150 was shared between DVT and PE, and miR-205 between DVT and VTE ( Figure 3 ). These patterns suggest that, although DVT, PE, and VTE share overlapping molecular pathways, many miRNAs may have condition-specific rather than universally applicable biomarker potential.

In our systematic review, the classification of miRNAs as prothrombotic or antithrombotic was based on the net reported effect on thrombus formation or burden in each source study, rather than on a single, direct molecular mechanism. This binary classification enabled us to pragmatically organize the reported miRNAs by simplifying a more complex biology. Many of the miRNAs discussed in this manuscript act primarily on endothelial repair, inflammation, angiogenesis, apoptosis, or immune (immunothrombotic) signaling rather than on the coagulation cascade itself. Furthermore, several miRNAs exhibit pleiotropic, context-dependent, and occasionally opposing effects across different experimental settings or VTE entities. The “unclassified” category reflects miRNAs for which the available evidence did not support a consistent net direction. These labels should therefore be read as descriptive summaries of predominant reported effects, not as fixed intrinsic properties.

Previous literature reviews and metanalyses have consistently described the circulating miRNAs as promising but not yet clinically validated biomarkers because most studies are small, heterogeneous, and lack standardized sampling, normalization, and external validation. These limitations make it difficult to determine whether altered miRNA levels contribute causally to thrombosis or merely reflect the thrombotic event [ 186 ]. Our systematic review extends these earlier reviews by evaluating 156 publications, separating evidence across DVT, PE, and VTE settings, and distinguishing clinical observations from functional and preclinical findings. The limited overlap of individual miRNAs across these entities supports the view that single miRNAs are unlikely to provide universally applicable biomarkers. Previous reviews have similarly proposed combining miRNA signatures with conventional biomarkers and incorporating them into existing VTE and cancer-associated thrombosis risk models [ 26 , 187 ]. These reviews also reinforce our pathway-based interpretation [ 188 , 189 ]. Related to this, cancer-associated thrombosis deserves particular consideration because tumor-derived factors, anticancer treatment, inflammation, and tissue-factor signaling create a distinct thrombotic environment [ 190 ].

In our systematic review, several miRNAs converged on shared molecular targets: ANGPT2 was targeted by prothrombotic miR-125a-5p and miR-542-3p; SIRT1 was regulated by miR-128-3p and miR-410-3p; and PTEN was influenced by both prothrombotic miRNAs (miR-499, miR-21, miR-221) and the antithrombotic miR-205. Some miRNAs demonstrated opposing effects across VTE contexts, highlighting the complex and context-dependent regulatory roles of miRNAs in thrombosis. Most miRNAs were examined in single studies with considerable methodological heterogeneity. A significant proportion relied on animal models, raising concerns about translatability to human VTE pathophysiology. Although many miRNAs are generally highly conserved across diverse species and share similar functions in target gene regulation, many miRNAs may not be conserved between distantly related species or even closely related species depending on the specific miRNA and species pair involved [ 191 ]. The conserved miRNAs do not necessarily exhibit the same expression levels or patterns in different species or at different stages within a species.

The identification of consistently significant miRNAs across multiple studies suggests diagnostic, prognostic, and therapeutic implications, particularly for prothrombotic miRNAs such as let-7b-5p, miR-28-3p, miR-125a-5p, miR-134, miR-190/miR-197, miR-195, miR-221, miR-320, and miR-1233, and antithrombotic miRNAs such as miR-26a, miR-34a-3p, miR-181b, miR-223, miR-145, and miR-150. Future research should prioritize human-specific models, standardized methodologies, and large-scale validation studies.

Across the reviewed literature, individual miRNAs converge on a limited set of recurring molecular pathways, which we summarize here rather than reiterating study-by-study findings. First, PI3K/Akt (and downstream mTOR) signaling recurs as a hub for endothelial and endothelial-progenitor-cell proliferation, migration, and thrombus recanalization, engaged by numerous miRNAs on both sides of the classification (e.g., via PTEN, a shared node targeted by prothrombotic miR-21/miR-221/miR-499 and antithrombotic miR-205). Second, NF-κB–driven inflammation and NLRP3 inflammasome activation define an immune-thrombosis axis linking endothelial injury, leukocyte activation, and cytokine release (e.g., miR-223, miR-448, miR-513c-5p, miR-22-3p). Third, a smaller group acts directly on the coagulation and fibrinolytic machinery such as tissue factor (miR-145, miR-185, miR-365a-3p), PAI-1 (miR-421), and antithrombin/SERPINC1 (miR-200c-3p, miR-141-3p), representing the most mechanistically proximal effects on thrombus formation. Fourth, endothelial repair and angiogenesis, frequently mediated through ANGPT2 and VEGFA, recur across EPC-focused studies. Finally, apoptosis and oxidative-stress pathways (Bcl-2 family, p53) modulate endothelial survival. Recognizing these convergent pathways provides more traceable targets for mechanistic and therapeutic investigation and helps explain the pleiotropy and context-dependence noted above.

The findings should be interpreted according to their level of evidence ( Supplementary Tables S2, S3, S4 and S5 ). The majority of the included studies were preclinical (in vitro and animal), and a large proportion of human studies were single-center case–control designs with limited sample sizes and without independent validation. The results of in vitro studies and animal findings should be regarded as hypothesis-generating, and greater confidence should be reserved for miRNAs in which concordant preclinical evidence is accompanied by validated human data.

The diagnostic estimates summarized here should also be interpreted with caution. Many derive from small, single-center, often retrospective cohorts without independent validation, a setting in which discrimination is systematically overestimated; near-perfect values, such as the reported AUC of 1.000 for miR-195, most likely reflect overfitting or small-sample optimism rather than genuine diagnostic accuracy. Moreover, few studies benchmarked miRNA performance against established diagnostics (D-dimer) or validated clinical probability scores (Wells, Geneva), and fewer still evaluated incremental value when added to these tools. Accordingly, the miRNAs discussed here should be regarded as exploratory biomarker candidates that require prospective, externally validated, and comparative evaluation before any diagnostic application can be considered.

Beyond the strength of the underlying associations, several practical barriers currently preclude the clinical translation of circulating-miRNA diagnostics in VTE. At the pre-analytical level, miRNA measurements are sensitive to the choice of matrix (serum versus plasma), to platelet and cellular contamination, and particularly to hemolysis, which spuriously elevates several red-cell–enriched miRNAs and can confound results if not controlled. At the analytical level, there is no consensus endogenous normalizer for circulating miRNAs, and quantification is platform-dependent (qRT-PCR, microarray, and next-generation sequencing yield non-interchangeable values), so results are frequently not reproducible across laboratories in the absence of standardized, validated assays. At the implementation level, miRNA assays remain more expensive and slower than D-dimer, and more importantly few studies have compared miRNAs against D-dimer or demonstrated their diagnostic value with validated clinical probability–based algorithms (e.g., Wells or Geneva scores). Until assay standardization, normalization, and prospective comparative validation are achieved, miRNAs are best regarded as complementary research tools rather than deployable clinical diagnostics.

5. Limitations

Several limitations should be acknowledged. First, the evidence base is dominated by preclinical (in vitro and animal) studies, and miRNA sequences and functions are not fully conserved across species, limiting translatability to human VTE. Second, most human studies were small, single-center, case–control investigations without independent validation cohorts, and the risk-of-bias appraisal ( Supplementary Table S2 ) indicated corresponding methodological concerns; reported diagnostic metrics such as AUCs should therefore be regarded as exploratory. Third, the human studies used heterogeneous biological matrices (serum, plasma, extracellular vesicles, mononuclear cells) and differing RNA-isolation and normalization strategies, which limits cross-study comparability. Fourth, the review was not prospectively registered, and no protocol was published; the search was restricted to PubMed and EMBASE and to English-language publications, which may have introduced selection and language bias, and a positive-result (publication) bias is likely in this literature. Finally, because of the pronounced heterogeneity of study designs and endpoints, a quantitative synthesis was not feasible, and no meta-analysis was performed.

6. Conclusions

This systematic review synthesized 156 studies investigating miRNAs in venous thromboembolism (VTE), including 99 studies of deep vein thrombosis (DVT), 25 of pulmonary embolism (PE), and 32 of VTE. The available evidence demonstrates that miRNAs are involved in several key biological pathways relevant to thrombogenesis, particularly endothelial dysfunction, inflammation and immunothrombosis, platelet activation, coagulation cascade activation, impaired fibrinolysis, angiogenesis, and vascular repair. These findings highlight the important role of miRNAs in the pathophysiology of VTE and identify multiple candidates with potential mechanistic and therapeutic relevance. Several circulating miRNAs have also demonstrated promising diagnostic performance in human studies; however, no circulating miRNA can currently be considered a sufficiently validated and reliable clinical biomarker of VTE. Most diagnostic findings are derived from relatively small, single-center studies without independent external validation, while substantial heterogeneity remains in biospecimen selection, RNA isolation, normalization strategies, and analytical platforms. Accordingly, the circulating miRNAs identified in this review should be regarded as promising biomarker candidates rather than established clinical biomarkers. Future research should prioritize adequately powered, prospective, multicenter human studies using standardized analytical approaches, with direct comparisons against D-dimer and established clinical diagnostic algorithms. Integrating functional and mechanistic investigations with well-characterized clinical datasets will be critical to establish the diagnostic, prognostic, and therapeutic utility of miRNA-based approaches and to facilitate their eventual translation into the management of VTE.

Acknowledgments

The authors thank Erin Healy Erickson for skillful assistance in preparing of this manuscript.

Abbreviations

Nomenclature

Gene symbols are presented in italics in accordance with standard gene nomenclature. For protein-coding genes, the encoded protein is listed below; noncoding genes are identified as producing non-protein-coding RNA. Standardized gene symbols are treated as nomenclature rather than manuscript abbreviations.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/jcm15166306/s1 .

Author Contributions

B.K. and H.N.E. contributed equally to this work as first authors. J.F. and W.K.J. contributed to conceptualization, methodology, supervision, and project administration. H.N.E. and B.K. conducted the investigation and data curation and prepared the original draft of the manuscript. F.S. was responsible for visualization and figure preparation. M.N., M.L., P.K., F.S., C.Z. and G.G. contributed to critical review and editing of the manuscript. All authors contributed to the review and editing of the manuscript and participated in validation of the work. All authors have read and agreed to the published version of the manuscript.

Data Availability Statement

All data is available as part of this case report and no additional source data are required.

Conflicts of Interest

The authors declare no conflicts of interests.

Funding Statement

This research received no external funding.

Footnotes

Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

References

1. Lutsey P.L., Zakai N.A. Epidemiology and prevention of venous thromboembolism. Nat. Rev. Cardiol. 2023;20:248–262. doi: 10.1038/s41569-022-00787-6.

2. Wendelboe A.M., Raskob G.E. Global Burden of Thrombosis: Epidemiologic Aspects. Circ. Res. 2016;118:1340–1347. doi: 10.1161/CIRCRESAHA.115.306841.

3. Bell E.J., Lutsey P.L., Basu S., Cushman M., Heckbert S.R., Lloyd-Jones D.M., Folsom A.R. Lifetime Risk of Venous Thromboembolism in Two Cohort Studies. Am. J. Med. 2016;129:339.E19–339.E26. doi: 10.1016/j.amjmed.2015.10.014.

4. Arnesen C.A.L., Veres K., Horváth-Puhó E., Hansen J.B., Sørensen H.T., Brækkan S.K. Estimated lifetime risk of venous thromboembolism in men and women in a Danish nationwide cohort: Impact of competing risk of death. Eur. J. Epidemiol. 2022;37:195–203. doi: 10.1007/s10654-021-00813-w.

5. Virani S.S., Alonso A., Aparicio H.J., Benjamin E.J., Bittencourt M.S., Callaway C.W., Carson A.P., Chamberlain A.M., Cheng S., Delling F.N., et al. Heart Disease and Stroke Statistics-2021 Update: A Report From the American Heart Association. Circulation. 2021;143:e254–e743. doi: 10.1161/CIR.0000000000000950.

6. Raskob G.E., Angchaisuksiri P., Blanco A.N., Büller H., Gallus A., Hunt B.J., Hylek E.M., Konstantinides S.V., McCumber M., Ozaki Y., et al. Thrombosis: A major contributor to global disease burden. Thromb. Res. 2014;134:931–938. doi: 10.1016/j.thromres.2014.08.014.

7. Zhen K., Tao Y., Xia L., Wang S., Gao Q., Wang D., Chen Z., Meng X., Kang Y., Fan G., et al. Epidemiology of pulmonary embolism in China, 2021: A nationwide hospital-based study. Lancet Reg. Health West. Pac. 2024;54:101258. doi: 10.1016/j.lanwpc.2024.101258.

8. Heit J.A., Silverstein M.D., Mohr D.N., Petterson T.M., O’Fallon W.M., Melton L.J., 3rd Predictors of survival after deep vein thrombosis and pulmonary embolism: A population-based, cohort study. Arch. Intern. Med. 1999;159:445–453. doi: 10.1001/archinte.159.5.445.

9. Søgaard K.K., Schmidt M., Pedersen L., Horváth-Puhó E., Sørensen H.T. 30-year mortality after venous thromboembolism: A population-based cohort study. Circulation. 2014;130:829–836. doi: 10.1161/CIRCULATIONAHA.114.009107.

10. Rabinovich A., Kahn S.R. How I treat the postthrombotic syndrome. Blood. 2018;131:2215–2222. doi: 10.1182/blood-2018-01-785956.

11. Sista A.K., Klok F.A. Late outcomes of pulmonary embolism: The post-PE syndrome. Thromb. Res. 2018;164:157–162. doi: 10.1016/j.thromres.2017.06.017.

12. Galanaud J.P., Monreal M., Kahn S.R. Epidemiology of the post-thrombotic syndrome. Thromb. Res. 2018;164:100–109. doi: 10.1016/j.thromres.2017.07.026.

13. Kahn S.R. Measurement properties of the Villalta scale to define and classify the severity of the post-thrombotic syndrome. J. Thromb. Haemost. JTH. 2009;7:884–888. doi: 10.1111/j.1538-7836.2009.03339.x.

14. Kahn S.R., Hirsch A.M., Akaberi A., Hernandez P., Anderson D.R., Wells P.S., Rodger M.A., Solymoss S., Kovacs M.J., Rudski L., et al. Functional and Exercise Limitations After a First Episode of Pulmonary Embolism: Results of the ELOPE Prospective Cohort Study. Chest. 2017;151:1058–1068. doi: 10.1016/j.chest.2016.11.030.

15. Ende-Verhaar Y.M., Cannegieter S.C., Vonk Noordegraaf A., Delcroix M., Pruszczyk P., Mairuhu A.T., Huisman M.V., Klok F.A. Incidence of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism: A contemporary view of the published literature. Eur. Respir. J. 2017;49:1601792. doi: 10.1183/13993003.01792-2016.

16. Barco S., Woersching A.L., Spyropoulos A.C., Piovella F., Mahan C.E. European Union-28: An annualised cost-of-illness model for venous thromboembolism. Thromb. Haemost. 2016;115:800–808. doi: 10.1160/TH15-08-0670.

17. Grosse S.D., Nelson R.E., Nyarko K.A., Richardson L.C., Raskob G.E. The economic burden of incident venous thromboembolism in the United States: A review of estimated attributable healthcare costs. Thromb. Res. 2016;137:3–10. doi: 10.1016/j.thromres.2015.11.033.

18. Konstantinides S.V., Meyer G., Becattini C., Bueno H., Geersing G.J., Harjola V.P., Huisman M.V., Humbert M., Jennings C.S., Jiménez D., et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS): The Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC) Eur. Respir. J. 2019;54:1901647. doi: 10.1183/13993003.01647-2019.

19. de Wit K., D’Arsigny C.L. Risk stratification of acute pulmonary embolism. J. Thromb. Haemost. JTH. 2023;21:3016–3023. doi: 10.1016/j.jtha.2023.05.003.

20. Yang P., Li H., Zhang J., Xu X. Research progress on biomarkers of pulmonary embolism. Clin. Respir. J. 2021;15:1046–1055. doi: 10.1111/crj.13414.

21. Shang R., Lee S., Senavirathne G., Lai E.C. microRNAs in action: Biogenesis, function and regulation. Nat. Rev. Genet. 2023;24:816–833. doi: 10.1038/s41576-023-00611-y.

22. Miranda K.C., Huynh T., Tay Y., Ang Y.S., Tam W.L., Thomson A.M., Lim B., Rigoutsos I. A pattern-based method for the identification of MicroRNA binding sites and their corresponding heteroduplexes. Cell. 2006;126:1203–1217. doi: 10.1016/j.cell.2006.07.031.

23. Vaghf A., Khansarinejad B., Ghaznavi-Rad E., Mondanizadeh M. The role of microRNAs in diseases and related signaling pathways. Mol. Biol. Rep. 2022;49:6789–6801. doi: 10.1007/s11033-021-06725-y.

24. Vishnoi A., Rani S. miRNA Biogenesis and Regulation of Diseases: An Updated Overview. Methods Mol. Biol. 2023;2595:1–12. doi: 10.1007/978-1-0716-2823-2_1.

25. Liu K., Tong H., Li T., Wang X., Chen Y. Research progress in molecular biology related quantitative methods of MicroRNA. Am. J. Transl. Res. 2020;12:3198–3211.

26. Luo M., Du M., Shu C., Liu S., Li J., Zhang L., Li X. The Function of microRNAs in Pulmonary Embolism: Review and Research Outlook. Front. Pharmacol. 2021;12:743945. doi: 10.3389/fphar.2021.743945. Corrigendum in Front. Pharmacol. 2022, 12, 822059. https://doi.org/10.3389/fphar.2021.822059 .

27. Bronze-da-Rocha E. MicroRNAs expression profiles in cardiovascular diseases. BioMed Res. Int. 2014;2014:985408. doi: 10.1155/2014/985408.

28. Teruel-Montoya R., Rosendaal F.R., Martínez C. MicroRNAs in hemostasis. J. Thromb. Haemost. JTH. 2015;13:170–181. doi: 10.1111/jth.12788.

29. Fernández-Hernando C., Suárez Y. MicroRNAs in endothelial cell homeostasis and vascular disease. Curr. Opin. Hematol. 2018;25:227–236. doi: 10.1097/MOH.0000000000000424.

30. De Los Reyes-García A.M., Arroyo A.B., Teruel-Montoya R., Vicente V., Lozano M.L., González-Conejero R., Martínez C. MicroRNAs as potential regulators of platelet function and bleeding diatheses. Platelets. 2019;30:803–808. doi: 10.1080/09537104.2018.1475635.

31. Page M.J., McKenzie J.E., Bossuyt P.M., Boutron I., Hoffmann T.C., Mulrow C.D., Shamseer L., Tetzlaff J.M., Akl E.A., Brennan S.E., et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ (Clin. Res. Ed.) 2021;372:n71. doi: 10.1136/bmj.n71.

32. Feng Y., Lei B., Zhang H., Niu L., Li X., Luo X., Zhang F. Long noncoding RNA TUG1 induces angiogenesis of endothelial progenitor cells and dissolution of deep vein thrombosis. Thromb. J. 2022;20:54. doi: 10.1186/s12959-022-00413-y.

33. Zhou K., Li N., Qi J., Tu P., Yang Y., Duan H. Diagnostic and prognostic potential of long non-coding RNA NORAD in patients with acute deep vein thrombosis and its role in endothelial cell function. Thromb. J. 2024;22:3. doi: 10.1186/s12959-023-00575-3.

34. Wang X., Zhang Z., Zheng W., Zhang B., Chu C., Chen J., Liu C., Xu K., Yu Z., Guo Q., et al. Macrophage Tim-4 protects against deep vein thrombosis by binding CK2β to suppress inflammatory responses. Front. Immunol. 2025;16:1634230. doi: 10.3389/fimmu.2025.1634230.

35. Xie X., Liu C., Lin W., Zhan B., Dong C., Song Z., Wang S., Qi Y., Wang J., Gu Z. Deep vein thrombosis is accurately predicted by comprehensive analysis of the levels of microRNA-96 and plasma D-dimer. Exp. Ther. Med. 2016;12:1896–1900. doi: 10.3892/etm.2016.3546.

36. Xu L., Ji C., Miao X., Ge J., Li F., Xu C. Combination of Circulating miR-125a-5p, miR-223-3p and D-dimer as a Novel Biomarker for Deep Vein Thrombosis. Am. J. Med. Sci. 2022;364:601–611. doi: 10.1016/j.amjms.2022.04.033.

37. Huang J., Wu X., Zhang Q., Yang L., Wan G., Zhang X., Wang Y., Zhao G. Depleted miR-125a-5p Causes Vascular Endothelial Cell Dysfunction in Deep Vein Thrombosis by Targeting Angiopoietin 2. Indian J. Hematol. Blood Transfus. Off. J. Indian Soc. Hematol. Blood Transfus. 2023;39:116–122. doi: 10.1007/s12288-022-01572-8.

38. Yu J., Jin Y., Xu C., Fang C., Zhang Z., Chen L., Xu G. Downregulation of miR-125a-5p Promotes Endothelial Progenitor Cell Migration and Angiogenesis and Alleviates Deep Vein Thrombosis in Mice Via Upregulation of MCL-1. Mol. Biotechnol. 2023;65:1664–1678. doi: 10.1007/s12033-023-00676-4.

39. Han J., Hao W., Ma Y., Hou Y. MiR-128-3p promotes the progression of deep venous thrombosis through binding SIRT1. Phlebology. 2023;38:540–549. doi: 10.1177/02683555231190268.

40. Zhang Y., Du X., Li W., Sang H., Qian A., Sun L., Li X., Li C. Resveratrol Improves Endothelial Progenitor Cell Function through miR-138 by Targeting Focal Adhesion Kinase (FAK) and Promotes Thrombus Resolution In Vivo. Med. Sci. Monit. Int. Med. J. Exp. Clin. Res. 2018;24:951–960. doi: 10.12659/msm.906116.

41. Wang S., Yang H., Wang F., Li L. LncRNA CASC2 mediates the lower extremity deep vein thrombosis via sponging miR-152-3p. J. Thromb. Thrombolysis. 2025;58:901–912. doi: 10.1007/s11239-025-03145-8.

42. Qin J., Liang H., Shi D., Dai J., Xu Z., Chen D., Chen X., Jiang Q. A panel of microRNAs as a new biomarkers for the detection of deep vein thrombosis. J. Thromb. Thrombolysis. 2015;39:215–221. doi: 10.1007/s11239-014-1131-0.

43. Mo J., Zhang D., Yang R. MicroRNA-195 regulates proliferation, migration, angiogenesis and autophagy of endothelial progenitor cells by targeting GABARAPL1. Biosci. Rep. 2016;36:e00396. doi: 10.1042/BSR20160139.

44. Qin J.Z., Wang S.J., Xia C. microRNAs regulate nitric oxide release from endothelial cells by targeting NOS3. J. Thromb. Thrombolysis. 2018;46:275–282. doi: 10.1007/s11239-018-1684-4.

45. Jin J., Wang C., Ouyang Y., Zhang D. Elevated miR-195-5p expression in deep vein thrombosis and mechanism of action in the regulation of vascular endothelial cell physiology. Exp. Ther. Med. 2019;18:4617–4624. doi: 10.3892/etm.2019.8166.

46. Tian X., Liu J., Jia W., Jiang P., Cheng Z., Zhang Y., Li J., Liu X., Tian C. MiR-197-3p affects angiogenesis and inflammation of endothelial cells by targeting CXCR2/COX2 axis. Am. J. Transl. Res. 2022;14:4666–4677.

47. Zhou S., Ma W., Li Y., Liu L., Lu S. Analysis of the predictive value of microRNA-199b-5p combined with nitric oxide for venous thrombosis in patients undergoing total knee arthroplasty. J. Orthop. Surg. Res. 2024;19:505. doi: 10.1186/s13018-024-04997-1.

48. Li Y., Ge J., Yin Y., Yang R., Kong J., Gu J. Upregulated miR-206 Aggravates Deep Vein Thrombosis by Regulating GJA1-Mediated Autophagy of Endothelial Progenitor Cells. Cardiovasc. Ther. 2022;2022:9966306. doi: 10.1155/2022/9966306.

49. Jiang Z., Ma J., Wang Q., Wu F., Ping J., Ming L. Combination of Circulating miRNA-320a/b and D-Dimer Improves Diagnostic Accuracy in Deep Vein Thrombosis Patients. Med. Sci. Monit. Int. Med. J. Exp. Clin. Res. 2018;24:2031–2037. doi: 10.12659/msm.906596.

50. Srivastava S., Garg I., Kumari B., Rai C., Singh Y., Kumar V., Yanamandra U., Singh J., Bansal A., Kumar B. Diagnostic potential of circulating micro RNA hsa-miR-320 in patients of high altitude induced deep vein thrombosis: An Indian study. Gene Rep. 2019;17:100550. doi: 10.1016/j.genrep.2019.100550.

51. Srivastava S., Garg I., Ghosh N., Varshney R. Therapeutic implication of MicroRNA-320a antagonist in attenuating blood clots formed during venous thrombosis. J. Thromb. Thrombolysis. 2024;57:699–709. doi: 10.1007/s11239-024-02947-6.

52. Tang J., Li C., Zhang P., Lin W., Yang Y. Predictive value of miR-374a-5p of peripheral blood mononuclear cells in deep venous thrombosis for elderly patients after total hip arthroplasty. Am. J. Transl. Res. 2021;13:10670–10675.

53. Zhang Y., Miao X., Zhang Z., Wei R., Sun S., Liang G., Li H., Chu C., Zhao L., Zhu X., et al. miR-374b-5p is increased in deep vein thrombosis and negatively targets IL-10. J. Mol. Cell. Cardiol. 2020;144:97–108. doi: 10.1016/j.yjmcc.2020.05.011.

54. Wang H., Lin S., Yang Y., Zhao M., Li X., Zhang L. Significant role of long non-coding RNA MALAT1 in deep vein thrombosis via the regulation of vascular endothelial cell physiology through the microRNA-383-5p/BCL2L11 axis. Bioengineered. 2022;13:13728–13738. doi: 10.1080/21655979.2022.2080412.

55. Wang X., Sundquist K., Elf J.L., Strandberg K., Svensson P.J., Hedelius A., Palmer K., Memon A.A., Sundquist J., Zöller B. Diagnostic potential of plasma microRNA signatures in patients with deep-vein thrombosis. Thromb. Haemost. 2016;116:328–336. doi: 10.1160/TH16-01-0071.

56. Xiao S., Wang C., Li Y., Zhang K., Jiao X., Zhao Z., Guo M., Liu B. Clinical significance and underlying mechanism of long non-coding RNA SNHG12 in lower extremity deep venous thrombosis. Clin. Transl. Sci. 2024;17:e70023. doi: 10.1111/cts.70023.

57. Wang P., Dai J., Li D. Peripheral Blood Levels of miR-448 and SIRT1 in Patients with Deep Venous Thrombosis and Their Relationship. Clin. Lab. 2022;68:2233. doi: 10.7754/Clin.Lab.2021.210638.

58. Wang T., Guan R., Xia F., Du J., Xu L. Curcumin promotes venous thrombi resolve process in a mouse deep venous thrombosis model via regulating miR-499. Microvasc. Res. 2021;136:104148. doi: 10.1016/j.mvr.2021.104148.

59. Guo Y., Yan L., Yang X., Fan C., Jianati R., Jia Y., Hao X., Ju F., Shi Z. MiR-503-5p as a potential biomarker for deep venous thrombosis (DVT) in multiple myeloma (MM) and its role in disease development. Ann. Hematol. 2025;104:6205–6214. doi: 10.1007/s00277-025-06720-4.

60. Lu Z., Wang S., Zhu X., Yuan X., Zhan Y., Li Y., Wang W. Resveratrol Induces Endothelial Progenitor Cells Angiogenesis via MiR-542-3p by Targeting Angiopoietin-2 and Involves in Recanalization of Venous Thrombosis. Med. Sci. Monit. Int. Med. J. Exp. Clin. Res. 2019;25:7675–7683. doi: 10.12659/MSM.917013.

61. Zhang Y., Zhang Z., Li H., Chu C., Liang G., Fan N., Wei R., Zhang T., Li L., Wang B., et al. Increased miR-6132 promotes deep vein thrombosis formation by downregulating FOXP3 expression. Front. Cardiovasc. Med. 2024;11:1356286. doi: 10.3389/fcvm.2024.1356286.

62. Kong L., Du X., Hu N., Li W., Wang W., Wei S., Zhuang H., Li X., Li C. Downregulation of let-7e-5p contributes to endothelial progenitor cell dysfunction in deep vein thrombosis via targeting FASLG. Thromb. Res. 2016;138:30–36. doi: 10.1016/j.thromres.2015.12.020.

63. Zhu J., Sun L.L., Li W.D., Li X.Q. Clarification of the Role of miR-9 in the Angiogenesis, Migration, and Autophagy of Endothelial Progenitor Cells Through RNA Sequence Analysis. Cell Transplant. 2020;29:963689720963936. doi: 10.1177/0963689720963936.

64. Zhou D.M., Sun L.L., Zhu J., Chen B., Li X.Q., Li W.D. MiR-9 promotes angiogenesis of endothelial progenitor cell to facilitate thrombi recanalization via targeting TRPM7 through PI3K/Akt/autophagy pathway. J. Cell. Mol. Med. 2020;24:4624–4632. doi: 10.1111/jcmm.15124.

65. Wang W., Yuan X., Xu A., Zhu X., Zhan Y., Wang S., Liu M. Human cancer cells suppress behaviors of endothelial progenitor cells through miR-21 targeting IL6R. Microvasc. Res. 2018;120:21–28. doi: 10.1016/j.mvr.2018.05.007.

66. Du X., Hong L., Sun L., Sang H., Qian A., Li W., Zhuang H., Liang H., Song D., Li C., et al. miR-21 induces endothelial progenitor cells proliferation and angiogenesis via targeting FASLG and is a potential prognostic marker in deep venous thrombosis. J. Transl. Med. 2019;17:270. doi: 10.1186/s12967-019-2015-z.

67. Qiao W., Niu L., Jiang W., Lu L., Liu J. Berberine ameliorates endothelial progenitor cell function and wound healing in vitro and in vivo via the miR-21-3p/RRAGB axis for venous leg ulcers. Regen. Ther. 2024;26:458–468. doi: 10.1016/j.reth.2024.06.011.

68. Wang Y., Liu Z., Li Y., Guo B., Liu Z., Zhang S., Zhao Y. Study on the mechanism of Huoxue Jiedu decoction in the intervention of phosphatidylinositol 3-kinase/serine-threonine kinase/nuclear factor-kappa B pathway in the treatment of deep vein thrombosis. J. Ethnopharmacol. 2026;355:120605. doi: 10.1016/j.jep.2025.120605.

69. Liang H., Chen Y., Li H., Yu X., Xia C., Ming Z., Zhong C. miR-22-3p Suppresses Endothelial Progenitor Cell Proliferation and Migration via Inhibiting Onecut 1 (OC1)/Vascular Endothelial Growth Factor A (VEGFA) Signaling Pathway and Its Clinical Significance in Venous Thrombosis. Med. Sci. Monit. Int. Med. J. Exp. Clin. Res. 2020;26:e925482. doi: 10.12659/MSM.925482.

70. Lou Z., Li X., Li C., Li X., Du K., Zhang F., Wang B. Microarray profile of circular RNAs identifies hsa_circ_000455 as a new circular RNA biomarker for deep vein thrombosis. Vascular. 2022;30:577–589. doi: 10.1177/17085381211016150.

71. Li Z., Ni J. Role of microRNA-26a in the diagnosis of lower extremity deep vein thrombosis in patients with bone trauma. Exp. Ther. Med. 2017;14:5069–5074. doi: 10.3892/etm.2017.5183.

72. Rahmanpour D., Fayaaz H., Shanehbandi D., Bornehdeli S., Jaberi M., Zarredar H., Zarrintan A. Microrna-26a confers a potential biomarker for screening of deep vein thrombosis. Gene Rep. 2022;27:101630. doi: 10.1016/j.genrep.2022.101630.

73. Lou Z., Ma H., Li X., Zhang F., Du K., Wang B. Hsa_circ_0001020 accelerates the lower extremity deep vein thrombosis via sponging miR-29c-3p to promote MDM2 expression. Thromb. Res. 2022;211:38–48. doi: 10.1016/j.thromres.2021.12.022.

74. Sun S., Chai S., Zhang F., Lu L. Overexpressed microRNA-103a-3p inhibits acute lower-extremity deep venous thrombosis via inhibition of CXCL12. IUBMB Life. 2020;72:492–504. doi: 10.1002/iub.2168.

75. Cao G., Zhou H., Wang D., Xu L. Knockdown of lncRNA XIST Ameliorates IL-1β-Induced Apoptosis of HUVECs and Change of Tissue Factor Level via miR-103a-3p/HMGB1 Axis in Deep Venous Thrombosis by Regulating the ROS/NF-κB Signaling Pathway. Cardiovasc. Ther. 2022;2022:6256384. doi: 10.1155/2022/6256384.

76. Zhang P., Zhao Q., Gong K., Long Y., Zhang J., Li Y., Guo X. Downregulation of miR-103a-3p Contributes to Endothelial Progenitor Cell Dysfunction in Deep Vein Thrombosis Through PTEN Targeting. Ann. Vasc. Surg. 2020;64:339–346. doi: 10.1016/j.avsg.2019.10.048.

77. Li H.Q., Pan Z.Y., Yang Z., Zhang D.B., Chen Q. Overexpression of MicroRNA-122 Resists Oxidative Stress-Induced Human Umbilical Vascular Endothelial Cell Injury by Inhibition of p53. BioMed Res. Int. 2020;2020:9791608. doi: 10.1155/2020/9791608.

78. Yang B., Zhang Z. Suppression of long intergenic non-protein coding RNA 1123 constrains lower extremity deep vein thrombosis via microRNA-125a-3p to target interleukin 1 receptor type 1. Bioengineered. 2022;13:13452–13461. doi: 10.1080/21655979.2022.2076496.

79. Meng Q., Wang W., Yu X., Li W., Kong L., Qian A., Li C., Li X. Upregulation of MicroRNA-126 Contributes to Endothelial Progenitor Cell Function in Deep Vein Thrombosis via Its Target PIK3R2. J. Cell. Biochem. 2015;116:1613–1623. doi: 10.1002/jcb.25115.

80. Chen L., Wang J., Wang B., Yang J., Gong Z., Zhao X., Zhang C., Du K. MiR-126 inhibits vascular endothelial cell apoptosis through targeting PI3K/Akt signaling. Ann. Hematol. 2016;95:365–374. doi: 10.1007/s00277-015-2567-9.

81. Zhu X., Jiang J., Wang J., Zhou Z., Ge X. Matrine Protects Endothelial Progenitor Cells against Apoptosis and Promotes Their Migration, Invasion, and Tube Formation Abilities via Modulating miR-126b/FOXO4 Axis. Pharmacology. 2023;108:331–343. doi: 10.1159/000527812.

82. Ou M., Hao S., Chen J., Zhao S., Cui S., Tu J. Downregulation of interleukin-6 and C-reactive protein underlies a novel inhibitory role of microRNA-136-5p in acute lower extremity deep vein thrombosis. Aging. 2020;12:21076–21090. doi: 10.18632/aging.103140.

83. Feng Y., Lei B., Zhang H., Niu L., Li X., Luo X., Zhang F. MicroRNA-136-5p from Endothelial Progenitor Cells-released Extracellular Vesicles Mediates TXNIP to Promote the Dissolution of Deep Venous Thrombosis. Shock. 2022;57:714–721. doi: 10.1097/SHK.0000000000001920.

84. Chen W., Zhu Y., Niu S., Zhou Y., Chang J., Gan S. Microarray profile of circular RNAs identifies CBT15_circR_28491 and T helper cells as new regulators for deep vein thrombosis. Front. Cardiovasc. Med. 2025;12:1578711. doi: 10.3389/fcvm.2025.1578711.

85. Zhang W., Chen P., Zong H., Ding Y., Yan R. MiR-143-3p targets ATG2B to inhibit autophagy and promote endothelial progenitor cells tube formation in deep vein thrombosis. Tissue Cell. 2020;67:101453. doi: 10.1016/j.tice.2020.101453.

86. Jha P.K., Vijay A., Prabhakar A., Chatterjee T., Nair V., Bajaj N., Kumar B., Sharma M., Ashraf M.Z. Transcriptome Profiling Reveals the Endogenous Sponging Role of LINC00659 and UST-AS1 in High-Altitude Induced Thrombosis. Thromb. Haemost. 2021;121:1497–1511. doi: 10.1055/a-1390-1713.

87. Sahu A., Jha P.K., Prabhakar A., Singh H.D., Gupta N., Chatterjee T., Tyagi T., Sharma S., Kumari B., Singh S., et al. MicroRNA-145 Impedes Thrombus Formation via Targeting Tissue Factor in Venous Thrombosis. eBioMedicine. 2017;26:175–186. doi: 10.1016/j.ebiom.2017.11.022.

88. Antoun C., Wikan V.E., Øverli Ø., Ueland T., Yeganeh G.J., Brækkan S.K., Brodin E., Hansen J.B. Plasma microRNA-145-5p as a diagnostic biomarker for acute deep vein thrombosis. Res. Pract. Thromb. Haemost. 2024;9:102671. doi: 10.1016/j.rpth.2024.102671.

89. Wang Y., Su Q., Tang H., Lin X., Yi Y., Tian Q., Luo Z., Fu M., Peng J., Zhang K. Circ-USP9X accelerates deep vein thrombosis after fracture by acting as a miR-148b-3p sponge and upregulates SRC kinase signaling inhibitor 1. Clinics. 2024;79:100403. doi: 10.1016/j.clinsp.2024.100403.

90. Wang W., Li C., Li W., Kong L., Qian A., Hu N., Meng Q., Li X. MiR-150 enhances the motility of EPCs in vitro and promotes EPCs homing and thrombus resolving in vivo. Thromb. Res. 2014;133:590–598. doi: 10.1016/j.thromres.2013.12.038.

91. Wang W., Zhu X., Du X., Xu A., Yuan X., Zhan Y., Liu M., Wang S. MiR-150 promotes angiogensis and proliferation of endothelial progenitor cells in deep venous thrombosis by targeting SRCIN1. Microvasc. Res. 2019;123:35–41. doi: 10.1016/j.mvr.2018.10.003.

92. Du X., Hu N., Yu H., Hong L., Ran F., Huang D., Zhou M., Li C., Li X. miR-150 regulates endothelial progenitor cell differentiation via Akt and promotes thrombus resolution. Stem Cell Res. Ther. 2020;11:354. doi: 10.1186/s13287-020-01871-9.

93. He X., Liu Y., Li Y., Wu K. Long non-coding RNA crnde promotes deep vein thrombosis by sequestering miR-181a-5p away from thrombogenic Pcyox1l. Thromb. J. 2023;21:44. doi: 10.1186/s12959-023-00480-9.

94. Zhang H., Xue T., Guo C., Wang Q., Yin H., Guo W. Exploration on the predictive value of MIR-181B for deep venous thrombosis of lower limbs after joint replacement. Acta Medica Mediterr. 2021;37:2729–2735.

95. Zhang D., Cheng C., Yang M., Zhang X., Yu X., Wang M. MicroRNA-181b-5p/HEY2 axis is involved in the progress of deep venous thrombosis via mediating vascular endothelial injury. Hematology. 2024;29:2423438. doi: 10.1080/16078454.2024.2423438.

96. Yang F., Chen D., Liu Y., Zhang X., Su Y., Zhang X., Yin Z., Wu J. Overexpression of MiR-181c-5p Attenuates Human Umbilical Vascular Endothelial Cell Injury in Deep Vein Thrombosis by Targeting FOS. Int. Heart J. 2023;64:759–767. doi: 10.1536/ihj.22-689.

97. Lu R., Zhu W., Sun H., Zhang L., Yu Z., Nie Z., Gao Y. Study on the Effect and Mechanism of miR-185 on Lower Extremity Deep Venous Thrombosis. Mol. Biotechnol. 2022;64:330–337. doi: 10.1007/s12033-021-00412-w.

98. Ni X., Yan J., Hu S., Wang X. MiR-199a target regulates TAB2 to promote the migration of endodermal progenitor cells and inhibit deep vein thrombosis in rats. Minerva Pediatr. 2023;75:150–152. doi: 10.23736/S2724-5276.22.07092-6.

99. Ding M., Chi G., Li F., Wang B., Shao C., Song W. Up-regulated miR-204-5p promoted the migration, invasion, and angiogenesis of endothelial progenitor cells to enhance the thrombolysis of rats with deep venous thrombosis by targeting SPRED1. Exp. Cell Res. 2022;411:112985. doi: 10.1016/j.yexcr.2021.112985.

100. Chen J., Zhang K., Yang Y., Wu J. MiR-204-5p regulates HUVEC cell inflammation and apoptosis by targeting P4HB. Cell. Mol. Biol. 2023;69:207–212. doi: 10.14715/cmb/2023.69.9.32.

101. Sun L.L., Xiao L., Du X.L., Hong L., Li C.L., Jiao J., Li W.D., Li X.Q. MiR-205 promotes endothelial progenitor cell angiogenesis and deep vein thrombosis recanalization and resolution by targeting PTEN to regulate Akt/autophagy pathway and MMP2 expression. J. Cell. Mol. Med. 2019;23:8493–8504. doi: 10.1111/jcmm.14739.

102. Wang S., Wang F., Ren J., Yang H. LncRNA NEAT1 Promotes Vascular Endothelial Cell Dysfunction via miR-218-5p/GAB2 and Serves as a Diagnostic Biomarker for Deep Vein Thrombosis. Clin. Appl. Thromb./Hemost. Off. J. Int. Acad. Clin. Appl. Thromb./Hemost. 2023;29:10760296231179447. doi: 10.1177/10760296231179447.

103. Li H.L., Liu Y.H., Shang X.B., Li Y., Feng L., Qi D.L. Effect of miR-223 on thrombophlebitis rats through regulating Toll-like receptor signaling pathway. Eur. Rev. Med. Pharmacol. Sci. 2020;24:2020–2027. doi: 10.26355/eurrev_202002_20380.

104. Sun L.L., Lei F.R., Jiang X.D., Du X.L., Xiao L., Li W.D., Li X.Q. LncRNA GUSBP5-AS promotes EPC migration and angiogenesis and deep vein thrombosis resolution by regulating FGF2 and MMP2/9 through the miR-223-3p/FOXO1/Akt pathway. Aging. 2020;12:4506–4526. doi: 10.18632/aging.102904.

105. Luo J., Lei Z., Zheng H., Zhou R. A novel role of miR-223-3p in reducing NLRP3-mediated inflammation and deep vein thrombosis in a mouse model. Sci. Prog. 2025;108:368504251337526. doi: 10.1177/00368504251337526.

106. Pan Z., Zhang Y., Li C., Yin Y., Liu R., Zheng G., Fan W., Zhang Q., Song Z., Guo Z., et al. MiR-296-5p ameliorates deep venous thrombosis by inactivating S100A4. Exp. Biol. Med. 2021;246:2259–2268. doi: 10.1177/15353702211023034.

107. Zhang J., Li M., Na X. LncRNA MEG8 promotes deep vein thrombosis by sponging miR-296-5p to regulate human umbilical vein endothelial cells. Hereditas. 2025;162:227. doi: 10.1186/s41065-025-00599-x.

108. Zhang Y., Zhang Z., Wei R., Miao X., Sun S., Liang G., Chu C., Zhao L., Zhu X., Guo Q., et al. IL (Interleukin)-6 Contributes to Deep Vein Thrombosis and Is Negatively Regulated by miR-338-5p. Arterioscler. Thromb. Vasc. Biol. 2020;40:323–334. doi: 10.1161/ATVBAHA.119.313137.

109. Pan Z., Chen Q., Ding H., Li H. MicroRNA-342-3p loaded by human umbilical cord mesenchymal stem cells-derived exosomes attenuates deep vein thrombosis by downregulating EDNRA. J. Thromb. Thrombolysis. 2022;54:411–419. doi: 10.1007/s11239-022-02694-6.

110. Yang X., Song Y., Sun Y., Wang M., Xiang Y. Down-regulation of miR-361-5p promotes the viability, migration and tube formation of endothelial progenitor cells via targeting FGF1. Biosci. Rep. 2020;40:BSR20200557. doi: 10.1042/BSR20200557.

111. Ai P., Shen B., Pan H., Chen K., Zheng J., Liu F. MiR-411 suppressed vein wall fibrosis by downregulating MMP-2 via targeting HIF-1α. J. Thromb. Thrombolysis. 2018;45:264–273. doi: 10.1007/s11239-017-1596-8.

112. Marchand A., Proust C., Morange P.E., Lompré A.M., Trégouët D.A. miR-421 and miR-30c inhibit SERPINE 1 gene expression in human endothelial cells. PLoS ONE. 2012;7:e44532. doi: 10.1371/journal.pone.0044532.

113. Chang Y., Wang C., Zheng Y., Wang Q. Circulating microRNA-423-5p serves as a potential diagnostic biomarker in elderly patients with deep-vein thrombosis. Int. J. Clin. Exp. Med. 2019;12:7065–7073.

114. Kong L., Hu N., Du X., Wang W., Chen H., Li W., Wei S., Zhuang H., Li X., Li C. Upregulation of miR-483-3p contributes to endothelial progenitor cells dysfunction in deep vein thrombosis patients via SRF. J. Transl. Med. 2016;14:23. doi: 10.1186/s12967-016-0775-2.

115. Fan J., Liu S., Ye W., Zhang X., Shi W. miR-483-5p-Containing exosomes treatment ameliorated deep vein thrombosis-induced inflammatory response. Eur. J. Pharm. Biopharm. 2024;202:114384. doi: 10.1016/j.ejpb.2024.114384.

116. Tang K.C., Yang Z.P., Zeng Q., Wang J., Guo F., Zhao Y. Effect of miR-495 on lower extremity deep vein thrombosis through the TLR4 signaling pathway by regulation of IL1R1. Biosci. Rep. 2018;38:BSR20180598. doi: 10.1042/BSR20180598.

117. Xu S., Yang Z., Li L., Cui Y., Chen Z. MiR-497-5p Ameliorates Deep Venous Thrombosis by Facilitating Endothelial Progenitor Cell Migration and Angiogenesis by Regulating LITAF. Biochem. Genet. 2025;63:4491–4506. doi: 10.1007/s10528-024-10927-x.

118. Chu C., Wang B., Zhang Z., Liu W., Sun S., Liang G., Zhang X., An H., Wei R., Zhu X., et al. miR-513c-5p Suppression Aggravates Pyroptosis of Endothelial Cell in Deep Venous Thrombosis by Promoting Caspase-1. Front. Cell Dev. Biol. 2022;10:838785. doi: 10.3389/fcell.2022.838785.

119. Zhu X., Chen B., Xu H. By modulating miR-525-5p/Bax axis, LINC00659 promotes vascular endothelial cell apoptosis. Immun. Inflamm. Dis. 2023;11:e764. doi: 10.1002/iid3.764.

120. Wang Q., Cheng G., Wang X., Wang D., Yang Y., Chen K., Ye J., Qing Z. Genetic effects of BDKRB2 and KNG1 on deep venous thrombosis after orthopedic surgery and the potential mediator. Sci. Rep. 2018;8:17332. doi: 10.1038/s41598-018-34868-9.

121. Qiu Y., Yang M., Che X., Yu X., Zhi K. miR-2467-3p/ABLIM1 Axis Mediates the Formation and Progression of Deep Vein Thrombosis by Regulating Inflammation and Oxidative Stress. Int. J. Angiol. 2024;33:174–181. doi: 10.1055/s-0044-1779663.

122. Li W.D., Zhou D.M., Sun L.L., Xiao L., Liu Z., Zhou M., Wang W.B., Li X.Q. LncRNA WTAPP1 Promotes Migration and Angiogenesis of Endothelial Progenitor Cells via MMP1 Through MicroRNA 3120 and Akt/PI3K/Autophagy Pathways. Stem Cells. 2018;36:1863–1874. doi: 10.1002/stem.2904.

123. Lu J., Fang Q., Ge X. Role and Mechanism of mir-5189-3p in Deep Vein Thrombosis of Lower Extremities. Ann. Vasc. Surg. 2021;77:288–295. doi: 10.1016/j.avsg.2021.07.004.

124. Wang Q., Chang Y., Yang X., Han Z. Deep sequencing of circulating miRNAs and target mRNAs level in deep venous thrombosis patients. IET Syst. Biol. 2023;17:212–227. doi: 10.1049/syb2.12071.

125. Jin Q.Q., Sun J.H., Du Q.X., Lu X.J., Zhu X.Y., Fan H.L., Hölscher C., Wang Y.Y. Integrating microRNA and messenger RNA expression profiles in a rat model of deep vein thrombosis. Int. J. Mol. Med. 2017;40:1019–1028. doi: 10.3892/ijmm.2017.3105.

126. Hao R., Li H., Li X., Liu J., Ji X., Zhang H., Zhang Z., Yang P., Zhai Z. Transcriptomic profiling of lncRNAs and mRNAs in a venous thrombosis mouse model. iScience. 2024;28:111561. doi: 10.1016/j.isci.2024.111561.

127. Zhang Y., Li J. Study on hsa_circ_101209 in Plasma of Pregnant Women with Deep Venous Thrombosis. Int. J. Gen. Med. 2025;18:209–219. doi: 10.2147/IJGM.S477830.

128. Pan B.Z., Luo Q.Y., Jiang M.J., Ning D., Deng L.M., Dai X.P., Wu Z.X., Deng Z.H., Luo D.Y., Wang Y.Y., et al. The molecular complexity of deep vein thrombosis was preliminarily explored based on the ceRNA network, scRNA-seq and AlphaFold 2. BMC Med. Genom. 2025;18:175. doi: 10.1186/s12920-025-02239-9.

129. Shi G., Shi X., Zhang M., Cheng R., Hu M., Zhao Y., Li S., Li X., Ma H., Li P. The underlying molecular mechanisms and biomarkers of Hip fracture combined with deep vein thrombosis based on self sequencing bioinformatics analysis. J. Orthop. Surg. Res. 2025;20:474. doi: 10.1186/s13018-025-05668-5.

130. Liu T.W., Liu F., Kang J. Let-7b-5p is involved in the response of endoplasmic reticulum stress in acute pulmonary embolism through upregulating the expression of stress-associated endoplasmic reticulum protein 1. IUBMB Life. 2020;72:1725–1736. doi: 10.1002/iub.2306.

131. Zhang Y., Tang S., Yang W., Du F. let-7b-5p suppresses the proliferation and migration of pulmonary artery smooth muscle cells via down-regulating IGF1. Clinics. 2022;77:100051. doi: 10.1016/j.clinsp.2022.100051.

132. Fabro A.T., Machado-Rugolo J., Baldavira C.M., Prieto T.G., Farhat C., Rotea ManGone F.R., Batah S.S., Cruvinel H.R., Aldá M.A., Monteiro J.S., et al. Circulating Plasma miRNA and Clinical/Hemodynamic Characteristics Provide Additional Predictive Information About Acute Pulmonary Thromboembolism, Chronic Thromboembolic Pulmonary Hypertension and Idiopathic Pulmonary Hypertension. Front. Pharmacol. 2021;12:648769. doi: 10.3389/fphar.2021.648769.

133. Liang D., Wen Z., Han W., Li W., Pan L., Zhang R. Curcumin protects against inflammation and lung injury in rats with acute pulmonary embolism with the involvement of microRNA-21/PTEN/NF-κB axis. Mol. Cell. Biochem. 2021;476:2823–2835. doi: 10.1007/s11010-021-04127-z.

134. Shen S., Yan B., Li Y., Jiang J. Berberine alleviates acute embolism-induced lung inflammation and injury by suppressing miR-22-5p expression and modulating the TLR4/NF-κB signaling pathway. Toxicol. Appl. Pharmacol. 2025;505:117563. doi: 10.1016/j.taap.2025.117563.

135. Wang Q., Ma J., Jiang Z., Wu F., Ping J., Ming L. Diagnostic value of circulating microRNA-27a/b in patients with acute pulmonary embolism. Int. Angiol. A J. Int. Union Angiol. 2018;37:19–25. doi: 10.23736/S0392-9590.17.03877-9.

136. Zhou X., Wen W., Shan X., Qian J., Li H., Jiang T., Wang W., Cheng W., Wang F., Qi L., et al. MiR-28-3p as a potential plasma marker in diagnosis of pulmonary embolism. Thromb. Res. 2016;138:91–95. doi: 10.1016/j.thromres.2015.12.006.

137. Mao H.Y., Liu L.N., Hu Y.M. Mesenchymal stem cells-derived exosomal miRNA-28-3p promotes apoptosis of pulmonary endothelial cells in pulmonary embolism. Eur. Rev. Med. Pharmacol. Sci. 2020;24:10619–10631. doi: 10.26355/eurrev_202010_23420.

138. Xiao J., Jing Z.C., Ellinor P.T., Liang D., Zhang H., Liu Y., Chen X., Pan L., Lyon R., Liu Y., et al. MicroRNA-134 as a potential plasma biomarker for the diagnosis of acute pulmonary embolism. J. Transl. Med. 2011;9:159. doi: 10.1186/1479-5876-9-159.

139. Zhou X., Wu Q., Hao T., Xu R., Hu X., Dong L. Expression and diagnostic value of circulating miRNA-190 and miRNA-197 in patients with pulmonary thromboembolism. J. Clin. Lab. Anal. 2021;35:e23574. doi: 10.1002/jcla.23574.

140. Liu T., Kang J., Liu F. Plasma Levels of microRNA-221 (miR-221) are Increased in Patients with Acute Pulmonary Embolism. Med. Sci. Monit. Int. Med. J. Exp. Clin. Res. 2018;24:8621–8626. doi: 10.12659/MSM.910893.

141. Tang L., Niu S., Xu J., Lu W., Zhou L. miR-221-3p is upregulated in acute pulmonary embolism complicated with pulmonary hypertension and promotes pulmonary arterial smooth muscle cells proliferation and migration by inhibiting PTEN. Cytotechnology. 2024;76:453–463. doi: 10.1007/s10616-024-00628-z.

142. Sun Y., Zhang X., Gao H., Liu M., Cao Q., Kang X., Wang Y., Zhu L. Expression of microRNA-514a-5p and its biological function in experimental pulmonary thromboembolism. Am. J. Transl. Res. 2019;11:5514–5530.

143. Kessler T., Erdmann J., Vilne B., Bruse P., Kurowski V., Diemert P., Schunkert H., Sager H.B. Serum microRNA-1233 is a specific biomarker for diagnosing acute pulmonary embolism. J. Transl. Med. 2016;14:120. doi: 10.1186/s12967-016-0886-9.

144. Peng L., Han L., Li X.N., Miao Y.F., Xue F., Zhou C. The Predictive Value of microRNA-134 and microRNA-1233 for the Early Diagnosis of Acute Exacerbation of Chronic Obstructive Pulmonary Disease with Acute Pulmonary Embolism. Int. J. Chronic Obstr. Pulm. Dis. 2020;15:2495–2503. doi: 10.2147/COPD.S266021.

145. Yang K., Li W., Duan W., Jiang Y., Huang N., Li Y., Ren B., Sun J. Resveratrol attenuates pulmonary embolism associated cardiac injury by suppressing activation of the inflammasome via the MALAT1-miR-22-3p signaling pathway. Int. J. Mol. Med. 2019;44:2311–2320. doi: 10.3892/ijmm.2019.4358.

146. Li Y., Shao J., Song J., Yu S., Wang J., Sun K. MiR-34a-3p suppresses pulmonary vascular proliferation in acute pulmonary embolism rat by targeting DUSP1. Biosci. Rep. 2022;42:BSR20210116. doi: 10.1042/BSR20210116.

147. Chen H., Ma Q., Zhang J., Meng Y., Pan L., Tian H. miR-106b-5p modulates acute pulmonary embolism via NOR1 in pulmonary artery smooth muscle cells. Int. J. Mol. Med. 2020;45:1525–1533. doi: 10.3892/ijmm.2020.4532.

148. Yang M.X., Wu Z.Z., Wu D.W., Liao X.Y., Wu Q.X., Shao N., Deng C.S. miR-124/PTBP1/PKM axis modulates pulmonary artery endothelial metabolism in a pulmonary thromboembolism rat model. J. Thorac. Dis. 2025;17:2217–2226. doi: 10.21037/jtd-24-1806.

149. Nafady A., Rashad A., Nafady-Hego H., Nasif K.A., Abbas A.M., Ahmed S.A., Mostafa A.T., Dongol E.M. Clinical Significance of miRNA-145 and -126 in Chronic Obstructive Pulmonary Disease with Pulmonary Embolism. Clin. Lab. 2022;68:1435. doi: 10.7754/Clin.Lab.2021.211113.

150. Jiang L., Li W., Gong X.L., Wang G.Y., Zhao F., Han L. Curcumin alleviates myocardial inflammation, apoptosis, and oxidative stress induced by acute pulmonary embolism by regulating microRNA-145-5P/insulin receptor substrate 1 axis. J. Physiol. Pharmacol. Off. J. Pol. Physiol. Soc. 2024;75:23–28. doi: 10.26402/jpp.2024.1.03.

151. Wu Y., Sun X., Cui G., Wang S. Mir-150-5p distinguishes acute pulmonary embolism, predicts the occurrence of pulmonary arterial hypertension, and regulates ox-LDL-induced endothelial cell injury. Hereditas. 2024;161:33. doi: 10.1186/s41065-024-00333-z.

152. Oto J., Plana E., Solmoirago M.J., Fernández-Pardo Á., Hervás D., Cana F., España F., Artoni A., Bucciarelli P., Carrabba G., et al. microRNAs and Markers of Neutrophil Activation as Predictors of Early Incidental Post-Surgical Pulmonary Embolism in Patients with Intracranial Tumors. Cancers. 2020;12:1536. doi: 10.3390/cancers12061536.

153. Zhu R., Qi W.Y., Liu T.W., Liu F. MicroRNA 449a can Attenuate Protective Effect of Urokinase Against Pulmonary Embolism. Front. Pharmacol. 2022;13:713848. doi: 10.3389/fphar.2022.713848.

154. Rossetti P., Goldoni M., Pengo V., Vescovini R., Mozzoni P., Tassoni M.I., Lombardi M., Rubino P., Bernuzzi G., Verzicco I., et al. MiRNA 126 as a New Predictor Biomarker in Venous Thromboembolism of Persistent Residual Vein Obstruction: A Review of the Literature Plus a Pilot Study. Semin. Thromb. Hemost. 2021;47:982–991. doi: 10.1055/s-0041-1726341.

155. Cao H.H., Zhang L.H., Chen H., Zhang W., Zhang Q., Liang X.D., Guo Y.Z., Tang P.F. Predicting Potential Targets of miR-130a in Venous Thromboembolism Based on a Target Score Method. Int. J. Hum. Genet. 2018;18:102–108. doi: 10.31901/24566330.2018/18.2.693.

156. Wang P., Zheng L., Qi X., Wang H., Zhang R., Song L., Chen R., Yan S., Chang W., Hu J., et al. Contribution of FOS in neutrophils to venous thromboembolism via miR-144 based on bioinformatic prediction and validation. J. Cell. Mol. Med. 2024;28:e18370. doi: 10.1111/jcmm.18370.

157. Fazzalari A., Basadonna G., Kucukural A., Tanriverdi K., Koupenova M., Pozzi N., Kakuturu J., Friedrich A.U., Korstanje R., Fowler N., et al. A Translational Model for Venous Thromboembolism: MicroRNA Expression in Hibernating Black Bears. J. Surg. Res. 2021;257:203–212. doi: 10.1016/j.jss.2020.06.027.

158. Jian X., Yang D., Wang L., Wang H. Downregulation of microRNA-200c-3p alleviates the aggravation of venous thromboembolism by targeting serpin family C member 1. Bioengineered. 2021;12:11156–11168. doi: 10.1080/21655979.2021.2005982.

159. Erhart F., Widhalm G., Kiesel B., Hackl M., Diendorfer A., Preusser M., Rössler K., Thaler J., Pabinger I., Ay C., et al. The plasma miRNome and venous thromboembolism in high-grade glioma: miRNA Sequencing of a nested case-control cohort. J. Cell. Mol. Med. 2024;28:e18149. doi: 10.1111/jcmm.18149.

160. Zhang M., Li J., Tai G., Li C., Wu H. Overexpression of miR-483-5p predicts venous thrombo-embolism onset in patients with lung cancer especially in high BMI cases. Acta Biochim. Pol. 2023;70:247–252. doi: 10.18388/abp.2020_6214.

161. Li C.T., Jiang X., He X.Q., Li D.Y., Chen S.H., Yao S.X., Zhang L., Zhao Z.R. Plasma microRNAs as potential biomarkers in diagnosis of acute venous thromboembolism. Clin. Hemorheol. Microcirc. 2023;84:435–448. doi: 10.3233/CH-231820.

162. Gabler J., Basílio J., Steinbrecher O., Kollars M., Kyrle P.A., Eichinger S. MicroRNA Signatures in Plasma of Patients With Venous Thrombosis: A Preliminary Report. Am. J. Med. Sci. 2021;361:509–516. doi: 10.1016/j.amjms.2020.12.002.

163. Zeng R., Song X.J., Liu C.W., Ye W. LncRNA ANRIL promotes angiogenesis and thrombosis by modulating microRNA-99a and microRNA-449a in the autophagy pathway. Am. J. Transl. Res. 2019;11:7441–7448.

164. Tian J., Adams M.J., Tay J.W.T., James I., Powell S., Hughes Q.W., Gilmore G., Baker R.I., Tiao J.Y. Estradiol-Responsive miR-365a-3p Interacts with Tissue Factor 3′UTR to Modulate Tissue Factor-Initiated Thrombin Generation. Thromb. Haemost. 2021;121:1483–1496. doi: 10.1055/a-1382-9983.

165. Lan H.T., Tong Z.J., Ma Y., Han H.T., Zhong M., Wang Z.H. Integrated Bioinformatics Analysis Identifies microRNA-200a-5p as a New Plasma Marker in Patients with Venous Thromboembolism. Ann. Vasc. Surg. 2022;84:354–370. doi: 10.1016/j.avsg.2022.02.027.

166. Wang Y., Zhang Z., Tao P., Reyila M., Qi X., Yang J. The Abnormal Expression of miR-205-5p, miR-195-5p, and VEGF-A in Human Cervical Cancer Is Related to the Treatment of Venous Thromboembolism. BioMed Res. Int. 2020;2020:3929435. doi: 10.1155/2020/3929435.

167. Chen X., Cao J., Ge Z., Xia Z. Correlation and integration of circulating miRNA and peripheral whole blood gene expression profiles in patients with venous thromboembolism. Bioengineered. 2021;12:2352–2363. doi: 10.1080/21655979.2021.1935401.

168. Morelli V.M., Snir O., Hindberg K.D., Hveem K., Brækkan S.K., Hansen J.B. High microRNA-145 plasma levels are associated with decreased risk of future incident venous thromboembolism: The HUNT study. Blood. 2024;143:1773–1781. doi: 10.1182/blood.2023022285.

169. Costa M.T., Neto B.V., da Silva J.B., Carvalho L., Salgado L., Pereira D., Adega F., Tavares V., Medeiros R. Venous Thrombogenesis and Cervical Cancer: Plasma MicroRNAs as Prognostic Indicators of Tumor Behavior. Int. J. Mol. Sci. 2025;26:9796. doi: 10.3390/ijms26199796.

170. Ciccacci C., Rufini S., Politi C., Novelli G., Forte V., Borgiani P. Could MicroRNA polymorphisms influence warfarin dosing? A pharmacogenetics study on mir133 genes. Thromb. Res. 2015;136:367–370. doi: 10.1016/j.thromres.2015.06.026.

171. Starikova I., Jamaly S., Sorrentino A., Blondal T., Latysheva N., Sovershaev M., Hansen J.B. Differential expression of plasma miRNAs in patients with unprovoked venous thromboembolism and healthy control individuals. Thromb. Res. 2015;136:566–572. doi: 10.1016/j.thromres.2015.07.005.

172. Wang X., Sundquist K., Svensson P.J., Rastkhani H., Palmér K., Memon A.A., Sundquist J., Zöller B. Association of recurrent venous thromboembolism and circulating microRNAs. Clin. Epigenet. 2019;11:28. doi: 10.1186/s13148-019-0627-z.

173. Kim J.O., Kim H.W., An H.J., Kim O.J., Oh J., Chong S.Y., Choi W.I., Oh D., Kim N.K. Association study of miR-146a, miR-149, miR-196a2, and miR-499 polymorphisms with venous thromboembolism in a Korean population. J. Thromb. Thrombolysis. 2019;47:255–262. doi: 10.1007/s11239-018-1778-z.

174. Ko E.J., Kim E.J., Kim J.O., Sung J.H., Park H.S., Ryu C.S., Oh J., Chong S.Y., Oh D., Kim N.K. Analysis of the Association Between MicroRNA Biogenesis Gene Polymorphisms and Venous Thromboembolism in Koreans. Int. J. Mol. Sci. 2019;20:3771. doi: 10.3390/ijms20153771.

175. Thibord F., Munsch G., Perret C., Suchon P., Roux M., Ibrahim-Kosta M., Goumidi L., Deleuze J.F., Morange P.E., Trégouët D.A. Bayesian network analysis of plasma microRNA sequencing data in patients with venous thrombosis. Eur. Heart J. Suppl. J. Eur. Soc. Cardiol. 2020;22:C34–C45. doi: 10.1093/eurheartj/suaa008.

176. Rodriguez-Rius A., Lopez S., Martinez-Perez A., Souto J.C., Soria J.M. Identification of a Plasma MicroRNA Profile Associated With Venous Thrombosis. Arterioscler. Thromb. Vasc. Biol. 2020;40:1392–1399. doi: 10.1161/ATVBAHA.120.314092.

177. Oto J., Navarro S., Larsen A.C., Solmoirago M.J., Plana E., Hervás D., Fernández-Pardo Á., España F., Kristensen S.R., Thorlacius-Ussing O., et al. MicroRNAs and Neutrophil Activation Markers Predict Venous Thrombosis in Pancreatic Ductal Adenocarcinoma and Distal Extrahepatic Cholangiocarcinoma. Int. J. Mol. Sci. 2020;21:840. doi: 10.3390/ijms21030840.

178. Anijs R.J.S., Laghmani E.H., Ünlü B., Kiełbasa S.M., Mei H., Cannegieter S.C., Klok F.A., Kuppen P.J.K., Versteeg H.H., Buijs J.T. Tumor-expressed microRNAs associated with venous thromboembolism in colorectal cancer. Res. Pract. Thromb. Haemost. 2022;6:e12749. doi: 10.1002/rth2.12749.

179. Fang N., Lai Z., Xu R., Huang P., Ye G., Lu W., Mo W., Zhang P. Small RNA Sequencing Reveals Exosomal miRNAs as Unique Feature Markers in Unprovoked Venous Thromboembolism. Acta Haematol. 2022;145:505–516. doi: 10.1159/000524569.

180. Ten Cate V., Rapp S., Schulz A., Pallares Robles A., Jurk K., Koeck T., Espinola-Klein C., Halank M., Seyfarth H.J., Beutel M.E., et al. Circulating microRNAs predict recurrence and death following venous thromboembolism. J. Thromb. Haemost. JTH. 2023;21:2797–2810. doi: 10.1016/j.jtha.2023.07.010.

181. Su Y., Li Q., Zheng Z., Wei X., Hou P. Identification of genes, pathways and transcription factor-miRNA-target gene networks and experimental verification in venous thromboembolism. Sci. Rep. 2021;11:16352. doi: 10.1038/s41598-021-95909-4.

182. Rouka E., Zarogiannis S.G., Hatzoglou C., Gourgoulianis K.I., Malli F. Identification of Genes and miRNAs Associated with TAFI-Related Thrombosis: An in Silico Study. Biomolecules. 2023;13:1318. doi: 10.3390/biom13091318.

183. Chanchal S., Sharma S., Mohd S., Sultan A., Mishra A., Ashraf M.Z. Unraveling Epigenetic Interplay between Inflammation, Thrombosis, and Immune-Related Disorders through a Network Meta-analysis. TH Open Companion J. Thromb. Haemost. 2024;8:e81–e92. doi: 10.1055/a-2222-9126.

184. Zhang L., Qin J., Li P. Bioinformatics analysis of potential common pathogenic mechanisms for COVID-19 and venous thromboembolism. Cytokine. 2024;181:156682. doi: 10.1016/j.cyto.2024.156682.

185. Lin Y., Wu J., Wang P., Lin X., Yang H. Identification of key genes related to lymphangiogenesis in venous thromboembolism through transcriptomics and verification by RT-qPCR. Front. Med. 2025;12:1659881. doi: 10.3389/fmed.2025.1659881.

186. Morelli V.M., Brækkan S.K., Hansen J.B. Role of microRNAs in Venous Thromboembolism. Int. J. Mol. Sci. 2020;21:2602. doi: 10.3390/ijms21072602.

187. Anijs R.J.S., Nguyen Y.N., Cannegieter S.C., Versteeg H.H., Buijs J.T. MicroRNAs as prognostic biomarkers for (cancer-associated) venous thromboembolism. J. Thromb. Haemost. JTH. 2023;21:7–17. doi: 10.1016/j.jtha.2022.09.001.

188. Huang S.L., Xin H.Y., Wang X.Y., Feng G.G., Wu F.Q., Feng Z.P., Xing Z., Zhang X.H., Xin H.W., Luo W.Y. Recent Advances on the Molecular Mechanism and Clinical Trials of Venous Thromboembolism. J. Inflamm. Res. 2023;16:6167–6178. doi: 10.2147/JIR.S439205.

189. Fang C., Huang F., Yao M., Wang Z., Ma J., Wu D., Guo T., Zhang F., Mo J. Advances in microRNA regulation of deep vein thrombosis through venous vascular endothelial cells (Review) Mol. Med. Rep. 2024;29:96. doi: 10.3892/mmr.2024.13220.

190. Tavares V., Neto B.V., Marques I.S., Assis J., Pereira D., Medeiros R. Cancer-associated thrombosis: What about microRNAs targeting the tissue factor coagulation pathway? Biochim. ET Biophys. Acta Rev. Cancer. 2024;1879:189053. doi: 10.1016/j.bbcan.2023.189053.

191. Singh G., Storey K.B. MicroRNA Cues from Nature: A Roadmap to Decipher and Combat Challenges in Human Health and Disease? Cells. 2021;10:3374. doi: 10.3390/cells10123374.

Associated Data

Supplementary Materials

Data Availability Statement

All data is available as part of this case report and no additional source data are required.