Key result
Circular RNAs modulate heart failure progression in preclinical models via microRNA sponging and stress signaling.
Why the study?
Circular RNAs are covalently closed non-coding RNAs with diverse regulatory functions, high stability, and tissue specificity that may regulate heart failure progression, prompting an examination of their biogenesis, mechanisms, biomarker potential, and therapeutic implications in acute and chronic heart failure.
Circular RNAs regulate key pathophysiological pathways in acute and chronic heart failure and represent promising candidates for biomarker development and targeted therapy, though rigorous clinical validation in large human cohorts is still required.
circRNAs may serve as HF biomarkers and targets; leaves open clinical translation pending prospective trials.
Circular RNAs (circRNAs) are covalently closed non-coding RNAs with diverse regulatory functions, high stability, and tissue specificity. This review examines their biogenesis, molecular mechanisms, experimental evidence, biomarker potential, and therapeutic implications in acute heart failure and chronic heart failure. By functioning as microRNA sponges, interacting with RNA-binding proteins, acting as protein scaffolds, undergoing cap-independent translation, and participating in stress-response signaling, circRNAs may regulate heart failure progression. Representative circRNAs, including circHIPK3, circSIRT1, circSLC8A1, circRNA-00203, and HRCR, have been linked to cardiomyocyte injury, calcium homeostasis, apoptosis, hypertrophy, fibrosis, inflammation, and ventricular remodeling. Circulating and exosome-derived circRNAs may also serve as biomarkers for diagnosis, prognosis, and disease monitoring. However, clinical translation remains limited by challenges in detection and standardization, low transcript abundance, tissue and cell heterogeneity, delivery efficiency, off-target effects, immunogenicity, and insufficient validation in large clinical cohorts. Most available evidence comes from preclinical models of myocardial infarction, pressure overload, and cardiac remodeling; evidence in heart failure with preserved ejection fraction , heart failure with mildly reduced ejection fraction, and large human populations remains limited. Overall, circRNAs provide new insights into heart failure pathophysiology and represent promising candidates for biomarker development and targeted therapy, but rigorous clinical validation is required before routine application.
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Zhao et al. (2026) conducted a review in Acute and chronic heart failure. Circular RNAs (circRNAs) was evaluated. Circular RNAs regulate acute and chronic heart failure progression via microRNA sponging, protein binding, and stress-response signaling in preclinical models, though clinical validation is needed.
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