Abstract
Cardiovascular diseases (CVDs) represent the predominant global health burden, where dysregulated programmed cell death (PCD) mechanisms critically drive myocardial injury pathogenesis. Circular RNAs (circRNAs), characterized by covalently closed structures conferring high stability, function as pivotal regulators coordinating cardiomyocyte fate through integrated networks encompassing ferroptosis, apoptosis, pyroptosis, autophagy, and necroptosis. This review synthesizes advances in understanding circRNA-mediated PCD modulation via molecular sponging, protein interactions, and epigenetic regulation. Key insights establish context-dependent circRNA functionality and validate circRNA-based diagnostic panels for CVDs stratification with enhanced accuracy. Therapeutically, viral vector-delivered protective circRNAs demonstrate significant efficacy in ameliorating post-infarction apoptosis and improving cardiac function. We further evaluate emerging CRISPR-based editing technologies and nanoplatform delivery systems for clinical translation, positioning circRNA networks as promising theranostic targets while highlighting unresolved questions regarding pathway crosstalk and tissue-specific delivery.