Circular RNAs in Cardiovascular Disease: From Pathophysiological Regulators to Novel Biotechnological Tools for Diagnosis and Therapy

Background: Cardiovascular diseases (CVDs) remain the leading cause of global mor-tality, creating an urgent need for innovative diagnostic and therapeutic strategies. Circular RNAs (circRNAs), a class of covalently closed non-coding RNAs, have recently emerged as critical regulators in cellular pathophysiology. Their unique structural sta-bility and tissue-specific expression patterns position them as highly promising molecules for biotechnological applications in cardiology. Methods: This review systematically synthesizes the current body of literature on circRNAs in the context of cardiovascular health and disease. We analyze their biogenesis, molecular mechanisms of action, and specific roles in key cardiac pathologies, including myocardial infarction, heart failure, and fibrosis. Furthermore, we evaluate the evidence supporting their use as clinical biomarkers and explore the cutting-edge technologies for their therapeutic delivery. Results: The evidence demonstrates that circRNAs function through diverse mechanisms, most notably as microRNA (miRNA) sponges and as scaffolds for RNA-binding proteins (RBPs), thereby modulating complex signaling networks that govern cardiomyocyte survival, apoptosis, inflammation, and regeneration. A multitude of specific circRNAs have been identified with dichotomous roles, either promoting or protecting against cardiac injury. Their exceptional stability in circulation supports their development as high-fidelity biomarkers, with meta-analyses confirming their diagnostic potential. Concurrently, advances in viral vectors, lipid nanoparticles (LNPs), and extracellular vesicles (EVs) are overcoming the critical hurdle of cardiac-specific delivery for circR-NA-based therapeutics. Conclusion: CircRNAs represent a paradigm-shifting class of molecules in cardiovascular medicine. They are no longer considered molecular curios-ities but are now recognized as fundamental regulators and powerful biotechnological tools. The convergence of circRNA biology with advanced nanodelivery platforms her-alds a new era of precision medicine, offering the potential to diagnose CVD earlier and develop novel therapies aimed at cardiac repair and regeneration.