Characterization of Systemic and Culprit-Coronary Artery miR-483-5p Expression in Chronic CAD and Acute Myocardial Infarction Male Patients

Author:

Volodko Olga12,Volinsky Natalia1,Yarkoni Merav3,Margalit Nufar1,Kusniec Fabio12,Sudarsky Doron12,Elbaz-Greener Gabby3ORCID,Carasso Shemy12ORCID,Amir Offer13

Affiliation:

1. The Lydia and Carol Kittner, Lea and Benjamin Davidai Division of Cardiovascular Medicine and Surgery and Research Institute, Tzafon Medical Center, Affiliated with Azrieli Faculty of Medicine, Bar Ilan University, Tiberias 1528001, Israel

2. The Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel

3. Heart Institute, Hadassah University Medical Center, Jerusalem, Department of Cardiology, Hadassah Medical Center, Faculty of Medicine, Hebrew University Jerusalem, Jerusalem 9574409, Israel

Abstract

Coronary artery disease (CAD) is the leading cause of mortality worldwide. In chronic and myocardial infarction (MI) states, aberrant levels of circulating microRNAs compromise gene expression and pathophysiology. We aimed to compare microRNA expression in chronic-CAD and acute-MI male patients in peripheral blood vasculature versus coronary arteries proximal to a culprit area. Blood from chronic-CAD, acute-MI with/out ST segment elevation (STEMI/NSTEMI, respectively), and control patients lacking previous CAD or having patent coronary arteries was collected during coronary catheterization from peripheral arteries and from proximal culprit coronary arteries aimed for the interventions. Random coronary arterial blood was collected from controls; RNA extraction, miRNA library preparation and Next Generation Sequencing followed. High concentrations of microRNA-483-5p (miR-483-5p) were noted as ‘coronary arterial gradient’ in culprit acute-MI versus chronic-CAD (p = 0.035) which were similar to controls versus chronic-CAD (p < 0.001). Meanwhile, peripheral miR-483-5p was downregulated in acute-MI and chronic-CAD, compared with controls (1.1 ± 2.2 vs. 2.6 ± 3.3, respectively, p < 0.005). A receiver operating characteristic curve analysis for miR483-5p association with chronic CAD demonstrated an area under the curve of 0.722 (p < 0.001) with 79% sensitivity and 70% specificity. Using in silico gene analysis, we detected miR-483-5p cardiac gene targets, responsible for inflammation (PLA2G5), oxidative stress (NUDT8, GRK2), apoptosis (DNAAF10), fibrosis (IQSEC2, ZMYM6, MYOM2), angiogenesis (HGSNAT, TIMP2) and wound healing (ADAMTS2). High miR-483-5p ‘coronary arterial gradient’ in acute-MI, unnoticed in chronic-CAD, suggests important local mechanisms for miR483-5p in CAD in response to local myocardial ischemia. MiR-483-5p may have an important role as a gene modulator for pathologic and tissue repair states, is a suggestive biomarker, and is a potential therapeutic target for acute and chronic cardiovascular disease.

Funder

The Ministry of Interior for the Development of Galilee North Israel

the Research Foundation of Poriya Medical Center

MIGAL

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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