Journal of molecular and cellular cardiology plus · 2026
Integrated heart-blood RNA editome profiling reveals circulating A-to-I editing candidates linked to dilated cardiomyopathy myocardial signatures and heart failure.
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Karagianni Korina, Topouzi Mantiana, Mitsi Ilektra, Sklaviadis Theodoros, Lazou Antigone, Dafou Dimitra
Аннотация
BACKGROUND: Dilated cardiomyopathy (DCM) is a leading cause of heart failure (HF), yet molecular signatures that are detectable in blood and mechanistically anchored in myocardial pathology remain limited. Adenosine-to-inosine (A-to-I) RNA editing is an important post-transcriptional regulator in the heart, but its biomarker potential in human DCM and its reflection in the circulation are not well defined.
METHODS: We performed comprehensive RNA editome profiling of human myocardium from DCM patients and non-failing donors, and integrated these results with peripheral blood RNA editing profiles from HF patients and controls, using a SPRINT-based pipeline with stringent in-house post-postprocessing and quality filtering. Global editing distributions and site-level differential editing were assessed, and shared heart-blood candidates were evaluated for directionality and functional enrichment.
RESULTS: Cardiac RNA editing was dominated by ADAR-mediated A-to-I events and was significantly increased in DCM, with prominent enrichment in Alu elements and a higher number of unique editing sites compared with controls. Site-level analysis identified a predominantly hyper-edited DCM signature, mapping to genes and pathways linked to cardiomyopathy and cellular stress, including hypoxia and apoptosis. Cross-tissue comparison revealed 107 shared differentially edited sites between DCM heart and HF blood, with subsets showing concordant directionality. Shared targets were enriched for innate immune and type I interferon signaling, RIG-I pathway regulation, hypoxia-related responses, and apoptosis.
CONCLUSIONS: DCM is associated with global myocardial A-to-I hyper-editing and a robust, multi-locus editing program. Importantly, a subset of these disease-associated editing events is detectable in peripheral blood from heart failure patients, supporting the feasibility of HF-associated circulating RNA editing signatures that reflect myocardial pathology.
METHODS: We performed comprehensive RNA editome profiling of human myocardium from DCM patients and non-failing donors, and integrated these results with peripheral blood RNA editing profiles from HF patients and controls, using a SPRINT-based pipeline with stringent in-house post-postprocessing and quality filtering. Global editing distributions and site-level differential editing were assessed, and shared heart-blood candidates were evaluated for directionality and functional enrichment.
RESULTS: Cardiac RNA editing was dominated by ADAR-mediated A-to-I events and was significantly increased in DCM, with prominent enrichment in Alu elements and a higher number of unique editing sites compared with controls. Site-level analysis identified a predominantly hyper-edited DCM signature, mapping to genes and pathways linked to cardiomyopathy and cellular stress, including hypoxia and apoptosis. Cross-tissue comparison revealed 107 shared differentially edited sites between DCM heart and HF blood, with subsets showing concordant directionality. Shared targets were enriched for innate immune and type I interferon signaling, RIG-I pathway regulation, hypoxia-related responses, and apoptosis.
CONCLUSIONS: DCM is associated with global myocardial A-to-I hyper-editing and a robust, multi-locus editing program. Importantly, a subset of these disease-associated editing events is detectable in peripheral blood from heart failure patients, supporting the feasibility of HF-associated circulating RNA editing signatures that reflect myocardial pathology.