Temporal changes in miR-23a-5p levels in subclinical atherosclerosis: A Potential biomarker

A high-cholesterol diet (HCD) is a well-established contributor to oxidative stress, inflammation, and atherogenesis, yet the temporal progression of these pathological changes and the regulatory role of circulating microRNAs (miRNAs) remain incompletely understood. In this study, we investigated the effects of prolonged HCD exposure to rats on lipid metabolism, oxidative stress, inflammation, endothelial dysfunction, and miRNA expression in a rat model. Male Wistar rats were fed either a standard diet or HCD for 30, 60, 90, or 120 days. Biochemical analyses revealed a progressive dyslipidemic profile characterized by elevated total cholesterol, triglycerides, LDL, VLDL, and atherogenic index, alongside a significant reduction in HDL. Lipid peroxidation levels increased markedly with HCD duration, while antioxidant markers PON1 and ApoA1 were significantly reduced and oxLDL levels were elevated. Inflammatory cytokines (CRP, TNF-α, IL-6, IL-8) and VCAM-1 were significantly increased, indicating systemic inflammation and endothelial activation. Notably, miR-23a-5p and miR-15b-5p were elevated in the serum of HCD-fed rats, with miR-23a-5p peaking at day 120. Correlation analyses revealed that miR-23a-5p expression positively correlated with oxLDL and inversely with ApoA1 and PON1 levels, suggesting its involvement in oxidative and lipoprotein dysregulation. These findings demonstrate that prolonged HCD induces a coordinated cascade of oxidative, inflammatory, and lipoprotein alterations, with miR-23a-5p emerging as promising biomarkers and potential regulators of redox and lipid homeostasis in atherogenesis.