Next generation MicroRNA sequencing to identify coronary artery disease patients at risk of recurrent myocardial infarction

Abstract

Background and aims: Variation in micro-RNA (miRNA) levels in blood has been associated with alterations of physiological functions of the cardiovascular system. Circulating miRNA have the potential to become reliable biomarkers for risk stratification and early detection of cardiovascular events. Recurrent thrombotic events in patients with established coronary artery disease (CAD) demonstrate the need for personalized approaches to secondary prevention, especially in light of recent novel treatment approaches. Methods: In a single center cohort study, whole blood samples were collected from 437 subjects undergoing cardiac catheterization, who were followed for recurrent cardiovascular events during a mean follow up of 1.5 years. We selected a case cohort (n = 22) with recurrent thrombotic events on standard medical therapy (stent thrombosis (n = 6) or spontaneous myocardial infarction (MI) (n = 16)) and a matched cohort with CAD, but uneventful clinical follow up (n = 26), as well as a control group with cardiovascular risk factors, but without angiographic CAD (n = 24). We performed complete miRNA next generation sequencing of RNA extracted from whole blood samples (including leukocytes and platelets). Results: A differential pattern of miRNA expression was found among controls, CAD patients with no events, and CAD patients with recurrent events. MiRNA previously associated with MI, CAD, endothelial function, vascular smooth muscle cells, platelets, angiogenesis, heart failure, cardiac hypertrophy, arrhythmia, and stroke were found variably expressed in our case-control cohorts. Seventy miRNA (FDR < 0.05) were linked to the risk of recurrent myocardial infarction and future stent thrombosis, as compared to CAD patients with subsequently uneventful follow up. Conclusions: MiRNA next generation sequencing demonstrates altered fingerprint profile of whole blood miRNA expression among subjects with subsequent recurrent thrombotic events on standard medical therapy (‘non-responders’), as compared to subjects with no recurrent cardiovascular events. MiRNA profiling may be useful to identify high risk subjects and provide additional insights into disease mechanisms not currently attenuated with standard medical therapy used in CAD treatment.

The Contrasting Role of Extracellular Vesicles in Vascular Inflammation and Tissue Repair

“…The improved ability to purify EVs and acquire accurate information about their numbers lends itself for the identification of new biomarkers, ones that were perhaps previously considered too dilute to be accurately quantified. More recent studies have exploited this to identify miRNAs with prognostic value for CVDs (Zampetaki et al, 2012;Jansen et al, 2014;Kanuri et al, 2018). Patient serum samples from the METEOR trial were tested for the levels of LDL-EVs and their protein content of von Willebrand factor (vWF), serpin C1, and plasminogen X.…”

In silico Prediction of miRNA Interactions With Candidate Atherosclerosis Gene mRNAs

“…In addition, miRNAs are considered novel non-invasive biomarkers of the instability of atherosclerotic plaques and have been associated ischemic disorders ( Churov et al, 2019 ). Their detection in the blood of patients may be a promising direction for the diagnosis of atherosclerosis complications such as ischemic stroke and myocardial infarction ( Kanuri et al, 2018 ; Desjarlais et al, 2019 ; Moghaddam et al, 2019 ; Vargas-Alarcon et al, 2019 ; Velle-Forbord et al, 2019 ; Wiese et al, 2019 ; Kondybayeva et al, 2020 ). When the pathogenic role of a specific miRNA is confirmed, it can be considered a potential therapeutic target ( Friedman et al, 2009 ; Fang et al, 2013 ; Moghaddam et al, 2019 ; Kazemi et al, 2020 ).…”

“…When the pathogenic role of a specific miRNA is confirmed, it can be considered a potential therapeutic target ( Friedman et al, 2009 ; Fang et al, 2013 ; Moghaddam et al, 2019 ; Kazemi et al, 2020 ). According to the miRBase database, miRNAs have been found in many human tissues and are able to regulate the expression of more than 60% of all protein-coding genes ( Kanuri et al, 2018 ; Ren et al, 2018 ; Wiese et al, 2019 ). Full complementarity between miRNA and mRNA results in degradation ( Leidinger et al, 2012 ; Alagia and Eritja, 2016 ).…”

Role of miRNAs induced by oxidized low-density lipoproteins in coronary artery disease: the REGICOR Study

“…These miRNAs have been associated with 1) apoptosis in ECs and cardiomyocytes (has-miR-16-5p, has-miR-499a-5p, has-miR-21-5p, has-miR-22-3p, and has-miR-125b-5p) [54][55][56][57]; 2) proliferation and differentiation in VSMCs and cardiomyocytes (has-miR-145-5p, has-miR-143-3p, and has-miR-133a-3p) [49,58,59]; 3) angiogenesis (has-miR-222-3p, and has-miR-22-3p) [58]; 4) secretion of pro-inflammatory cytokines (has-miR-186-5p, All rights reserved. No reuse allowed without permission.…”