miR‑18a‑5p Serves as a Diagnostic and Prognostic Biomarker and Attenuates Hypoxia‑Induced Cardiac Microvascular Endothelial Injury by Targeting the HIF1A/NF‑κB Pathway in Chronic Heart Failure.

PURPOSE: Chronic heart failure (CHF) is a severe end-stage cardiovascular syndrome with high mortality and poor prognosis. This study aimed to investigate the expression, diagnostic, and prognostic value of serum miR-18a-5p in CHF patients and to explore its molecular mechanism in regulating hypoxia-induced injury.

METHODS

A total of 125 CHF patients and 125 healthy controls were enrolled. The expression of miR-18a-5p was detected by RT-qPCR. The diagnostic efficacy was evaluated by the ROC curve. The prognostic value was analyzed by Kaplan-Meier survival analysis and multivariate Cox regression. Human cardiac microvascular endothelial cells (hCMECs) were used to establish a hypoxic injury model. Cell viability, apoptosis, and inflammatory cytokines were measured by CCK-8, flow cytometry, and ELISA. The targeting relationship between miR-18a-5p and HIF1A was verified by a dual-luciferase reporter assay. The expression of apoptosis, fibrosis, and NF-κB pathway proteins was detected by RT-qPCR and Western blot.

RESULTS

In patients with CHF, circulating miR‑18a‑5p was markedly downregulated, exhibiting a diagnostic AUC value of 0.874. Diminished miR‑18a‑5p expression was closely linked to decreased LVEF, increased levels of BNP and cTnI, higher NYHA classification, and a poorer long‑term prognosis. miR-18a-5p was a protective factor for CHF. In vitro, overexpression of miR-18a-5p enhanced cell viability, inhibited apoptosis, reduced the secretion of pro-inflammatory factors, and downregulated collagen I, collagen III, and α-SMA expression in hypoxic hCMECs. miR-18a-5p targeted HIF1A 3'UTR and negatively regulated HIF1A/NF-κB signaling. Overexpression of HIF1A reversed the protective effects of miR-18a-5p.

CONCLUSION

miR-18a-5p attenuates hypoxia-induced inflammation, apoptosis, and fibrosis by targeting the HIF1A/NF-κB pathway. Circulating miR-18a-5p therefore holds promising clinical prospects as a non-invasive serum biomarker for CHF diagnosis and risk stratification. Upregulation of miR-18a-5p provides a potential molecular strategy for preventing hypoxia-mediated cardiac microvascular remodeling in chronic heart failure.