Circular RNAs as Biomarkers and Therapeutic Targets in Diabetic Cardiovascular Complications

Abstract

Background: The global prevalence of diabetes mellitus (DM) is rising rapidly and is projected to reach unprecedented levels by 2035 and 2050, with a disproportionate burden among elderly populations and in low- and middle- income countries. Diabetes- related cardiovascular complications remain a leading cause of morbidity and mortality despite advances in glycaemic control and pharmacotherapy. There is an urgent need for novel molecular biomarkers and therapeutic targets to improve early detec tion, risk stratification, and personalised management. Methods: A comprehensive narrative review of the current literature was conducted to summarise emerging evidence on the biological roles of circular RNAs (circRNAs) in diabetes and its cardiovascular complications. Published experimental, trans lational, and clinical studies investigating circRNA expression, mechanisms of action, and therapeutic potential were critically analysed. Results: CircRNAs have emerged as key regulators in the pathophysiology of diabetes- associated cardiovascular disorders, in cluding diabetic cardiomyopathy, endothelial dysfunction, and vascular inflammation, as well as related microvascular compli cations. Mechanistically, circRNAs act through diverse pathways such as microRNA sponging, modulation of gene transcription, interaction with RNA- binding proteins, and regulation of cellular processes including apoptosis, fibrosis, oxidative stress, and inflammation. Their covalently closed structure confers exceptional stability, while their tissue- and disease- specific expression profiles support their utility as sensitive biomarkers for early diagnosis, prognosis, and therapeutic monitoring. Advances in synthetic circRNA design further highlight their promise as novel therapeutic agents, although challenges related to delivery efficiency, specificity, and off- target effects remain.