Clin Cardiol. 2026 Nov;49(11):e70502. doi: 10.1002/clc.70502.

ABSTRACT

BACKGROUND: Cardiac fibrosis, characterized by excessive extracellular matrix (ECM) deposition, contributes to adverse cardiac remodeling and heart failure. Circular RNAs (circRNAs) have emerged as regulators of fibrotic processes, with potential applications in cardiovascular diagnosis and therapy. This review examines the molecular mechanisms through which circRNAs regulate cardiac fibrosis and evaluates their potential as diagnostic biomarkers and therapeutic targets.

METHODS: A comprehensive literature search was conducted using PubMed and Scopus to identify studies investigating the roles of circRNAs in cardiac fibrosis, including their molecular mechanisms, diagnostic potential, and therapeutic applications. Relevant experimental and clinical studies were examined.

RESULTS: Experimental evidence implicates circRNAs in cardiac fibroblast activation, myofibroblast differentiation, and ECM remodeling through microRNA-mediated regulation and interactions with profibrotic signaling pathways, including TGF-β/SMAD and Wnt/β-catenin. circSMAD4, circHelz, and circHIPK3 have been associated with profibrotic responses, whereas circNFIB and circCDR1 have demonstrated antifibrotic effects in experimental models. Modulation of circRNA expression has attenuated fibrosis and improved cardiac function in selected animal studies. The structural stability and tissue-specific expression of circRNAs also support their investigation as potential circulating biomarkers. However, clinical evidence remains limited, and therapeutic translation faces challenges related to targeted delivery, off-target effects, immunogenicity, and tissue specificity.

CONCLUSIONS: CircRNAs are important regulators of cardiac fibrosis and represent promising candidates for diagnostic biomarker development and targeted antifibrotic therapy. Despite encouraging preclinical findings, further clinical research is needed to establish their diagnostic validity, safety, and therapeutic efficacy in humans.

PMID:43023673 | DOI:10.1002/clc.70502