Circulating Extracellular miRNA Analysis in Patients with Stable CAD and Acute Coronary Syndromes

Abstract

Extracellular circulating microRNAs (miRNAs) are currently a focus of interest as non-invasive biomarkers of cardiovascular pathologies, including coronary artery disease (CAD) and acute coronary syndromes (ACS): myocardial infarction with and without ST-segment elevation (STEMI and NSTEMI) and unstable angina (UA). However, the current data for some miRNAs are controversial and inconsistent, probably due to pre-analytical and methodological variances in different studies. In this work, we fulfilled the basic pre-analytical requirements provided for circulating miRNA studies for application to stable CAD and ACS research. We used quantitative PCR to determine the relative plasma levels of eight circulating miRNAs that are potentially associated with atherosclerosis. In a cohort of 136 adult clinic CAD patients and outpatient controls, we found that the plasma levels of miR-21-5p and miR-146a-5p were significantly elevated in ACS patients, and the level of miR-17-5p was decreased in ACS and stable CAD patients compared to both healthy controls and hypertensive patients without CAD. Within the ACS patient group, no differences were found in the plasma levels of these miRNAs between patients with positive and negative troponin, nor were any differences found between STEMI and NSTEMI. Our results indicate that increased plasma levels of miR-146a-5p and miR-21-5p can be considered general ACS circulating biomarkers and that lowered miR-17-5p can be considered a general biomarker of CAD.

MicroRNA-146a Serves as a Biomarker for Adverse Prognosis of ST-Segment Elevation Myocardial Infarction

“…MiR-146a has been shown to be significantly expressed in atherosclerotic arteries ( 32 ). There is also evidence that miR-146a is expressed not only in endothelial cells and smooth muscle cells but also in cardiomyocytes ( 33 ). Etiologies of STEMI include rupture of local vulnerable plaques and cardiomyocyte necrosis.…”

Current Knowledge of MicroRNAs (miRNAs) in Acute Coronary Syndrome (ACS): ST-Elevation Myocardial Infarction (STEMI)

“…Lower levels of miR-26a and miR-191 were found in the plasma of individuals with acute MI [111]. Using cDNA synthesis and quantitative PCR, plasma levels of miR-21-5p and miR-146a-5p were significantly elevated in patients with ACS [22]. Expressions of miR-30d-5p, miR-146a-5p, and miR-23a-3p were statistically lower in patients with STEMI compared with the control group patients.…”

“…Interestingly, only the combination of miR-146a and miR-21 were independent predictors of LV remodeling [135]. One study reveals that miR-146a-5p is significantly elevated in patients with ACS [22], while on the contrary, miR-146a-5p was also detected statistically lower in patients with STEMI compared with the control group patients [112].…”

“…In consideration of their roles, steadily growing research in life science of the expression pattern of cardiac tissue reveals that microRNAs (miRNAs/miR) are up-or downregulated during myocardial injury, showing their potential as biomarkers for AMI and ischemia-reperfusion injury (I/R) [17,18]. Accordingly, the gamut of new evidence lays out the potential role of miRNAs as novel biomarkers in acute and chronic cardiovascular diseases such as stable CAD [17,[19][20][21][22], acute coronary syndromes (NSTEMI/STEMI) [23][24][25][26], or heart failure (HF) and cardiac remodeling secondary to MI [27,28].…”

DataSheet2.ZIP

“…Interestingly, we found that hsa-miR-17-5p, hsa-miR-20b-5p and hsa-miR-27a-3p co-regulated by these two DElncRNAs have important biological roles in CHD. The expression of hsa-miR-17-5p is down-regulation in patients with CHD, which could be as a biomarker of CHD (Zhelankin et al, 2021) and a good predictor of the severity of coronary atherosclerosis (Chen et al, 2015). In addition, lncRNA SNHG16 could regulate NF-κB signaling pathway by binding hsa-miR-17-5p, and then affect proliferation and inflammatory response in atherosclerosis patients, which provide a potential target for treating AS (An et al, 2019).…”