A specific molecular signature of extra-vesicles (EVs) was associated with cardiometabolic risk profile and atherosclerotic burden in patients with chronic coronary syndrome: a pilot study

Abstract

Abstract Background microRNAs (miRs) are pivotal regulators of mRNA and protein expression. They critically contribute to cardiovascular pathophysiology and circulate in the blood using extra-vesicles (EVs) as delivery carrier. The role of EV-associated miRs in atherosclerotic cardiovascular disease, however, is unclear. Purpose The aim of this study was to detect Coronary Artery Disease (CAD)-related miRs carried by EVs in stable patients with Chronic Coronary Syndrome (CCS). In particular we aimed to assess whether a specific miRs signature is associated with the cardiometabolic risk profile and coronary atherosclerotic burden and plaque features, as evaluated by coronary computed tomography angiography (CTA) in these patients. Methods miRs with known effects in the cardiovascular system were analysed by real time-PCR in EVs isolated from CCS patients by density gradient centrifugation (n=21). All patients underwent coronary CTA to assess total, calcified, and noncalcified plaque volume (PV). Obstructive CAD was defined as the presence of stenoses >50% in at least one of the main coronary vessels. Results All CCS patients (n=21) were statin users and had coronary atherosclerosis documented by coronary CTA. Among the 25 miRs tested, 7 were detected within EVs and 4 of them, miR-145-5p, miR-30e5-p, miR-126-5p, miR-375, were significantly related with cardiometabolic profile, showing an alternative association with glucose and insulin, a positive correlation with HDL-Cholesterol and a negative correlation with triglycerides, BMI and waist circumference. No association was observed with Total-Cholesterol and LDL-Cholesterol (Figure1). These miRs were also not associated with the presence of obstructive CAD, but were significantly related with total, calcified, and noncalcified PVs (Figure1). Conclusions In CCS patients, among the 25 miRs studied and out of the 7 EV-associated, only 4 miRs were related with a specific cardiometabolic risk profile, characterized by insulin-resistance, obesity, high triglyceride and low HDL-Cholesterol levels. They were also associated with an increased coronary atherosclerotic burden. These results suggest a potential involvement of specific EV-associated miRs in molecular mechanisms of residual atherosclerotic risk.Figure 1