The cardiovascular benefits of glucagon-like peptide-1 receptor agonists as novel diabetes drugs are mediated via the suppression of miR-203a-3p and miR-429 expression

Abstract

Abstract Purpose Coronary artery disease (CAD) is associated with a high fatality rate and a heavy global health care burden. Glucagon-like peptide-1 (GLP-1) exerts positive cardiovascular effects, although the molecular mechanisms are unclear. Therefore, this study aimed to verify whether the cardioprotective effects of GLP-1 are mediated through the regulation of micro-RNA (miRNA) expression. Materials and Methods Follow-up assessments were conducted for 116 patients with type 2 diabetes alone (controls) and 123 patients with both type 2 diabetes and CAD. After matching, each group comprised 63 patients, and age, body mass index, and serum levels of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and haemoglobin A1C were compared. Subsequently, the expression profiles of four circulating miRNAs (miR-203a-3p, miR-429, miR-205-5p, and miR-203b-5p) were assessed via qRT-PCR in the 63 patients with diabetes and CAD between six months (baseline) and twelve months after the initiation of GLP-1 therapy. Results As expected, the metabolic factors were significantly improved after 6 months of treatment with GLP-1 compared with pre-treatment values, and the expression levels of two of the miRNAs (miR-203a-3p and miR-429) decreased from baseline levels in those with diabetes and CAD. Conclusions The results suggest that the cardiovascular benefits induced by GLP-1 are mediated via suppressed expression of two miRNAs: miR-203a-3p and miR-429.