MicroRNA expression profile of human advanced coronary atherosclerotic plaques

Mariana S Parahuleva,Bernhard Schieffer,Rainer Schulz,Gerhild Euler,Hans Hölschermann,Christoph Lipps,Behnoush Parviz

doi:10.1038/s41598-018-25690-4

Abstract

MicroRNA (miR) is reported to be involved in vascular inflammation and may represent a novel class of diagnostic biomarkers in cardiovascular disease. We aimed to identify the miR expression profile in human advanced coronary atherosclerotic plaques (CAP) and to connect this expression to the processes in atherosclerosis. Microarray techniques and TaqMan polymerase chain reaction were used to analyse the global expression of 352 miRs in CAP obtained during ACS MULTI-LINK study. 11 miRs were selected on the basis of their implication in atherosclerosis, endothelial activation, and inflammation. 6 miRs were found to be differently expressed in CAP when compared to non-atherosclerotic internal mammary arteries (IMA, p < 0.05). The expression of miR-21, -92a, and -99a was verified and found to be significantly up-regulated in CAP versus IMA (p < 0.001). We also performed bioinformatic analysis and found several potential target genes of miR-92a and -99a as well as several pathways with impact on atherosclerosis which could be differently expressed due to this miRNA profile. The most up-regulated miRs are involved in processes known to be connected to atherosclerosis. Interfering with the miR expression in the artery wall is a potential way to affect atherosclerotic plaque and cardiovascular disease development.

Highlights

Monocytes/macrophages play important roles in the formation of atherosclerotic lesions[1,2]
Based on the microarray data we focused on miRs, which were robustly expressed across all investigated groups and profoundly different between patients with acute coronary syndrome (ACS) and healthy controls
In silico analysis of miRs (n = 39) was performed by database screening (TargetScan.org, miRBa-se.org, microRNA.org) to determine relevant miRNA biomarker candidates according to their predicted interactions with molecules of interest, and conduction of careful in silico analysis, studying the literature for relevant miRs associated with vascular inflammation and atherosclerosis, cardiovascular pathogenesis, including endothelial injury, endothelial activation, and vascular inflammation[21], as well as the impact of their target genes on plaque growth and stability was considered

Summary

Introduction

Monocytes/macrophages play important roles in the formation of atherosclerotic lesions[1,2]. Advanced vulnerable plaques are rich in inflammatory cells, mostly only ‘classically polarized’ macrophages, and are highly susceptible to rupture[4,5]. These plaques represent a high risk with the standard invasive diagnosis by coronary angiography. No information is currently available with respect to cellular miRs expression and their modulation in human coronary atherosclerotic lesions under inflammatory condition during the early phase of AMI development in vivo and this will be the object of this case-control study. Our observations will identify plaques miRNA candidates, which are correlated with early acute phase of myocardial infarction and vascular inflammation and may help to develop future diagnostic and therapeutic abilities to identify and evaluate cardiovascular disease and particular ACS

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Conclusion