Hayes Penelope¹, Myers Jason², Ford Aurora³, Hamilton Jaxon⁴, Graham Bella⁵, Sullivan Miles⁶, Wallace Lucy⁷, Woods Samuel⁸, Coleen Riley⁹
ABSTRACT:
Cardiac ischemia-reperfusion injury (IRI) remains a major challenge in acute coronary syndromes and cardiac surgery, contributing significantly to final infarct size and clinical outcomes. This review comprehensively evaluates the emerging roles of non-coding RNAs (ncRNAs) — including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) — as diagnostic biomarkers and therapeutic targets in IRI. We analyze: (1) mechanistically validated ncRNAs regulating key IRI pathways (apoptosis, inflammation, calcium handling), (2) their release kinetics and stability in circulating biofluids, and (3) clinical studies correlating ncRNA levels with infarct size, LV dysfunction, and cardioprotective intervention efficacy. Special emphasis is placed on multi-ncRNA panels for early diagnosis and their potential to guide personalized reperfusion strategies. Current limitations in extracellular vesicle isolation techniques and ncRNA quantification are critically discussed, along with future directions in RNA-based therapeutics and point-of-care testing platforms.