Molecular Network Approach Reveals As a Central Target of Cardiac ProtectomiRs

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2021 Sep 10

PMID 34502448

Citations 7

Authors

Andras Makkos

Bence Agg

Zoltan V Varga

Zoltan Giricz

Mariann Gyongyosi

Dominika Lukovic

Rainer Schulz

Monika Bartekova

Aniko Gorbe

Peter Ferdinandy

Affiliations

Soon will be listed here.

Abstract

Cardioprotective medications are still unmet clinical needs. We have previously identified several cardioprotective microRNAs (termed ProtectomiRs), the mRNA targets of which may reveal new drug targets for cardioprotection. Here we aimed to identify key molecular targets of ProtectomiRs and confirm their association with cardioprotection in a translational pig model of acute myocardial infarction (AMI). By using a network theoretical approach, we identified 882 potential target genes of 18 previously identified protectomiRs. The gene was the most central and it was ranked first in the protectomiR-target mRNA molecular network with the highest node degree of 5. Therefore, and its targeting microRNAs were further validated in heart samples obtained from a translational pig model of AMI and cardioprotection induced by pre- or postconditioning. Three out of five -targeting pig homologue of rat ProtectomiRs showed significant upregulation in postconditioned but not in preconditioned pig hearts. was downregulated at the mRNA and protein level in ischemic postconditioning but not in ischemic preconditioning. This is the first demonstration that is the central molecular target of ProtectomiRs and that decreased expression may regulate ischemic postconditioning-, but not preconditioning-induced acute cardioprotection. We conclude that is a potential novel drug target for acute cardioprotection.

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