Association between miR-146a and Tumor Necrosis Factor Alpha (TNF-alpha) in Stable Coronary Artery Disease

Background and Objectives: Tumor necrosis factor alpha (TNF-alpha) is proatherogenic and associated with the risk of acute ischemic events, although the mechanisms that regulate TNF-alpha expression in stable coronary artery disease (SCAD) are not fully understood. We investigated whether metabolic, inflammatory, and epigenetic (microRNA (miRNA)) markers are associated with TNF-alpha expression in SCAD. Materials and Methods: Patients with SCAD were prospectively recruited and their metabolic and inflammatory profiles were assessed. TNF-alpha levels were assessed using an enzyme-linked immunosorbent assay. The relative expression of six circulating miRNAs associated with the regulation of inflammation and/or atherosclerosis was determined. Results: Of the 24 included patients with the mean age of 65 (9) years, 88% were male, and 54% were diabetic. The TNF-alpha levels were (median (interquartile range)) 1.0 (0.7-1.1) pg/mL. The percentage of glycosylated hemoglobin (r = 0.418, p = 0.042), serum triglyceride levels (r = 0.429, p = 0.037), and C-reactive protein levels (r = 0.407, p = 0.048) were positively correlated with TNF-alpha levels. Of the candidate miRNAs, miR-146a expression levels were negatively correlated with TNF-alpha levels (as indicated by r = 0.500, p = 0.035 for correlation between delta cycle threshold (Delta C-t) miR-146a and TNF-alpha levels). In multivariate analysis, serum triglyceride levels and miR-146a expression levels were independently associated with TNF-alpha levels. miR-146 expression levels were not associated with metabolic or other inflammatory parameters and were negatively correlated with the number of coronary vessels with obstructive disease (as indicated by r = 0.556, p = 0.017 for correlation between Delta C-t miR-146a and number of diseased vessels). Conclusions: miR-146a expression levels were negatively correlated with TNF-alpha levels in patients with SCAD, irrespective of other metabolic or inflammatory markers, and with the severity of coronary artery disease. The results add to the knowledge on the role of miR-146a in TNF-alpha-based inflammation in SCAD and support future research on the potential therapeutic use of miR-146a in such a clinical scenario.