Effect of Hypoxia-Induced MicroRNA-210 Expression on Cardiovascular Disease and the Underlying Mechanism

Abstract

Cardiovascular diseases have high morbidity and mortality rates worldwide, and their treatment and prevention are challenging. MicroRNAs are a series of noncoding RNAs with highly conserved sequences and regulate gene expression by inhibiting mRNA transcription or degrading targeting proteins. MicroRNA-210 is significantly upregulated during hypoxia and plays a protective role by inhibiting apoptosis and regulating cell proliferation, differentiation, migration, mitochondrial metabolism, and angiogenesis in hypoxic cells. MicroRNA-210 expression is altered in cardiovascular diseases such as atherosclerosis, acute myocardial infarction, preeclampsia, aortic stenosis, and heart failure, and overexpression of microRNA-210 in some of these diseases exerts protective effects on target organs. Furthermore, chronically upregulated miR-210 potentially plays a marked pathogenic role in specific situations. This review primarily focuses on the upstream pathways, downstream targets, clinical progress in cardiovascular disease, and potential applications of microRNA-210.

Hypoxia-Induced miR-210 Is Necessary for Vascular Regeneration upon Acute Limb Ischemia

“…MiR-210 seems to play a role not only in the acute response to hypoxia/ischemia, but also in the following phases when the vascular network is regenerated, re-establishing oxygen and nutrient supply [19]. Indeed, in vitro data show that miR-210 induces capillary-like structures formation and endothelial cell migration [6,15,19]. This evidence prompted studies aimed at demonstrating the ability of miR-210 to stimulate angiogenesis in ischemic disease models.…”

MicroRNA‐129‐1‐3p protects cardiomyocytes from pirarubicin‐induced apoptosis by down‐regulating the GRIN2D‐mediated Ca2+ signalling pathway

“…[17][18][19] Several miRNAs have been implicated in cardiotoxicity caused by anthracyclines. miRNAs have been shown to regulate cardiac physiology and pathology.…”

“…[17][18][19] Several miRNAs have been implicated in cardiotoxicity caused by anthracyclines. 18,19 We recently performed a microarray analysis on myocardial miR-NAs in a rat model of THP-induced myocardial injury and identified 78 dysregulated miRNAs in the THP group compared with control (P < .05, |log2(fold change) | > 0.585), of which 50 were up-regulated and 28 were down-regulated. 23 Additional in vitro and in vivo studies have implicated miR-532-3p, miR-34a-5p and miR-451 in DOX-induced cardiotoxicity.…”

“…miRNAs have been shown to regulate cardiac physiology and pathology. [17][18][19] Several miRNAs have been implicated in cardiotoxicity caused by anthracyclines. 20,21 For example, miR-21 prevents DOX-induced cardiomyocyte apoptosis by targeting BTG2, 22 while miR-208a mediates DOX-induced cardiotoxicity through regulating GATA4.…”

“…23 Additional in vitro and in vivo studies have implicated miR-532-3p, miR-34a-5p and miR-451 in DOX-induced cardiotoxicity. 18,19 We recently performed a microarray analysis on myocardial miR-NAs in a rat model of THP-induced myocardial injury and identified 78 dysregulated miRNAs in the THP group compared with control (P < .05, |log2(fold change) | > 0.585), of which 50 were up-regulated and 28 were down-regulated. 24 In this study, we performed Gene Ontology (GO) enrichment analysis of the 28 miRNAs down-regulated by THP using databases in the public domain (http://www.mirba se.org/, http:// www.micro rna.gr/LncBa se/, https ://david.ncifc rf.gov/, and http:// www.targe tscan.org/vert_71/).…”