Circular RNAs and endothelial dysfunction: mechanistic crosstalk and emerging therapeutic perspectives

The dysfunction of endothelial cells (ECs) plays an essential role in the pathogenesis and development of a wide range of complex human diseases. These cells are important for regulating the functions of capillaries. Alterations in the vascular endothelium are associated with a broad spectrum of diseases, including atherosclerosis, stroke, hypertension, diabetes, coronary artery disease (CAD), venous thrombosis, cancer, and related angiogenesis disorders. Consequently, impaired endothelial function is recognized as a characteristic feature of numerous human diseases. circular RNAs (circRNAs) have recently expanded recognition as critical contributors to cellular processes, and their potential implications in endothelial dysfunction-related diseases have gained interest. While studies have extensively explored the roles of non-coding RNAs in endothelial dysfunction-related disease, the understanding of circRNAs in this context remains unclear. In this review, we aim to shed light on the mechanisms of circRNAs and their effect on endothelial dysfunction-related diseases. The investigation of circRNAs in endothelial dysfunction-related diseases such as atherosclerosis, hypertension, diabetes, and CAD holds great promises for uncovering innovative insights into disease pathogenesis and developing novel therapeutic approaches. • This review explores the regulatory functions of circRNAs in endothelial dysfunction. • circRNAs are highlighted as key modulators of diverse endothelial dysfunction-related processes, including CAD, stroke, cancer, hypertension, angiogenesis, cellular senescence, and atherosclerosis. • Unique circRNA expression profiles are observed in atherosclerosis, hypertension, CAD, and diabetes, highlighting their importance as disease-specific molecular markers. • circRNAs exert their effects through multiple mechanisms, including miRNA sponging, modulation of transcription, and interaction with RNA-binding proteins to effect key signaling cascades. • Several circRNAs demonstrate clinical relevance as sensitive and specific biomarkers, offering new targets for early diagnosis and therapeutic intervention in endothelial dysfunction-related vascular diseases.