Association of whole blood microRNA expression with platelet function and turnover in patients with coronary artery disease

Abstract

Introduction: The risk of recurrent cardiovascular events in patients with coronary artery disease (CAD) is determined by multiple factors including platelet function and turnover. MicroRNAs (miRs) may regulate both platelet function and turnover. We aimed to identify candidate miRs associating with platelet function and turnover in a cohort of stable CAD patients. Furthermore, we retrieved information on binding targets of the candidate miRs to obtain a more comprehensive biological insight into miR regulation of platelet function and turnover. Methods: Based on existing literature and a pilot study, we identified nine candidate miRs. Subsequently, we investigated the expression of the candidate miRs in whole blood and their relation to platelet function and turnover in 749 CAD patients. Platelet function was analysed using impedance aggregometry, optical aggregometry and serum thromboxane B2 measurements. Platelet turnover markers (immature platelet count, immature platelet fraction and mean platelet volume) were measured using monochromatic automated flow cytometry. Results: Expression of miR-93-5p, miR-126-3p, miR-150-5p, miR-423-3p and miR-1180-3p showed negative correlations with platelet function (p-values from <0.0001 to 0.0006, rho from −0.13 to −0.36). In addition, expression of miR-423-3p showed negative correlation with platelet turnover markers (p-values from 0.001 to 0.004, rho from −0.11 to −0.12). Conclusions: We identified several novel miRs that may regulate platelet function and turnover, thereby contributing to the increased risk of recurrent cardiovascular events in CAD patients.