COMPARATIVE ANALYSIS OF MIRNA REGULATORY PATHWAYS IN ATHEROSCLEROSIS: UNRAVELLING SIMILARITIES AND DIVERGENCES ACROSS DIFFERENT STAGES AND PHENOTYPES

Background: Atherosclerosis remains a leading cause of cardiovascular morbidity and mortality worldwide, contributing to life-threatening complications such as coronary artery disease, myocardial infarction, stroke, and peripheral vascular disease. Despite well-established risk factors such as hyperlipidemia, hypertension, oxidative stress, and inflammation, the molecular underpinnings of plaque development and progression are still being elucidated. Among the emerging regulators, microRNAs (miRNAs)—short, non-coding RNAs—have gained recognition for their ability to post-transcriptionally modulate gene expression and influence vascular cell behavior and immune responses. Objective: This review aims to explore the regulatory role of miRNAs in the initiation, progression, and phenotypic diversification of atherosclerotic plaques, and to evaluate their potential as diagnostic biomarkers and therapeutic targets. Main Discussion Points: The review discusses the involvement of miRNAs in endothelial dysfunction, lipid accumulation, foam cell formation, and plaque instability. It highlights the differential expression of key miRNAs such as miR-92a, miR-126, miR-155, and miR-221 across various stages and phenotypes of atherosclerosis. Methodological approaches including next-generation sequencing, in vivo animal models, and integrative omics analyses are reviewed. The role of genetic polymorphisms and environmental stimuli in modulating miRNA expression is also addressed. Conclusion: miRNAs serve as central regulators in the complex pathophysiology of atherosclerosis, with distinct expression profiles correlating with disease stage and vascular phenotype. Their diagnostic and therapeutic potential warrants further investigation through well-designed clinical studies to enable their translation into clinical practice.