全血微小RNA表达与冠心病患者血小板功能及周转率的关联

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

作者信息

Pedersen Oliver Buchhave, Hvas Anne-Mette, Grove Erik Lerkevang, Larsen Sanne Bøjet, Pasalic Leonardo, Kristensen Steen Dalby, Nissen Peter H

机构信息

Thrombosis and Haemostasis Research Unit, Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark; Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.

Thrombosis and Haemostasis Research Unit, Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark.

出版信息

Thromb Res. 2022 Mar;211:98-105. doi: 10.1016/j.thromres.2022.01.026. Epub 2022 Jan 29.

DOI:10.1016/j.thromres.2022.01.026

PMID:35149399

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 B 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.

摘要

引言

冠状动脉疾病（CAD）患者复发性心血管事件的风险由多种因素决定，包括血小板功能和更新。微小RNA（miR）可能同时调节血小板功能和更新。我们旨在确定一组稳定CAD患者中与血小板功能和更新相关的候选miR。此外，我们检索了候选miR的结合靶点信息，以更全面地了解miR对血小板功能和更新的调节作用。

方法

基于现有文献和一项初步研究，我们确定了9个候选miR。随后，我们调查了749例CAD患者全血中候选miR的表达及其与血小板功能和更新的关系。使用阻抗聚集法、光学聚集法和血清血栓素B测量分析血小板功能。使用单色自动流式细胞术测量血小板更新标志物（未成熟血小板计数、未成熟血小板分数和平均血小板体积）。

结果

miR-93-5p、miR-126-3p、miR-150-5p、miR-423-3p和miR-1180-3p的表达与血小板功能呈负相关（p值从<0.0001至0.0006，rho从-0.13至-0.36）。此外，miR-423-3p的表达与血小板更新标志物呈负相关（p值从0.001至0.004，rho从-0.11至-0.12）。