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Review
. 2011 Oct;80(4):558-64.
doi: 10.1124/mol.111.073528. Epub 2011 Jul 7.

MicroRNAs: new players in cardiac injury and protection

Rakesh C Kukreja  1 , Chang Yin, Fadi N Salloum
Affiliations
Review

MicroRNAs: new players in cardiac injury and protection

Rakesh C Kukreja et al. Mol Pharmacol. 2011 Oct.

Abstract

MicroRNAs (miRNAs) have emerged as a novel class of endogenous, small, noncoding RNAs that negatively regulate gene expression via degradation or translational inhibition of their target mRNAs. Over 700 miRNAs have been identified and sequenced in humans, and the number of miRNA genes is estimated at more than 1000. Individual miRNA is functionally important as a transcription factor because it has the ability to regulate the expression of multiple genes through binding to its target with imperfect or perfect complement. In the heart, miRNAs have been involved in several clinical scenarios, such as ischemia/reperfusion (I/R) injury and heart failure suggesting that regulation of their function could be used as a novel cardioprotective strategy. In particular, miRNA-1, miRNA-21, miRNA-24, miRNA-29, miRNA-92a, miRNA-126, miRNA-133, miRNA-320, miRNA-199a, miRNA-208, and miRNA-195 have been shown to be regulated after I/R injury. Because tissue miRNAs can be released into circulating blood, they also offer exciting new opportunities for developing sensitive biomarkers, including miRNA-1, miRNA-126, miR-208, and miRNA-499, for acute myocardial infarction and other cardiac diseases.

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Figures

Fig. 1.
Fig. 1.
Schematic diagram showing dynamics of microRNAs during myocardial infarction and protective strategies including ischemic preconditioning, heat shock, hypoxia and pharmacologic preconditioning, with potential utilization of synthetic miRNAs and/or antagomirs.
Fig. 2.
Fig. 2.
Induction of miRs by ischemic preconditioning (IPC) and Effect of miR on myocardial infarct size after ischemia/reperfusion. A, infarct size reduction after IPC (n = 6/group). B, gel electrophoresis image of RT-PCR products of miRNAs. C, average normalized results showing increase in miR-1, miR-21, and miR-24 after IPC. The results are means ± S.E.M. from three independent hearts. D, reduction of myocardial infarct size (percentage of risk area) after direct delivery of IPC-miRNA into the heart. *, P < 0.05 versus saline control and non-IPC miRNA-treated hearts. E, uptake of miR-21 after injection in LV wall. Gel electrophoresis image of the RT-PCR for miR-21. F, average normalized changes in miR-21. Endogenous U1A small nuclear RNA (RNU1A) was used as control. [Reprinted from Yin C, Salloum FN, and Kukreja RC (2009) A novel role of microRNA in late preconditioning: upregulation of endothelial nitric oxide synthase and heat shock protein 70. Circ Res 104:572–575. Copyright © 2009 American Heart Association. Used with permission.].
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