Ischemic Postconditioning-Mediated miRNA-21 Protects against Cardiac ischemia/reperfusion Injury via PTEN/Akt Pathway
Open Access
- 3 October 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (10), e75872
- https://doi.org/10.1371/journal.pone.0075872
Abstract
Ischemic postconditioning (IPost) protects the reperfused heart from infarction which has drawn much attention recently. However, studies to date have rarely investigated the role of microRNAs (miRNAs) in IPost. The aims of this study were to investigate whether miR-21 is involved in the protective effect of IPost against myocardial ischemia-reperfusion (I/R) injury and disclose the potential molecular mechanisms involved. We found that miR-21 was remarkably up-regulated in mouse hearts after IPost. To determine the protective role of IPost-induced miR-21 up-regulation, the mice were divided into the following four groups: I/R group; I/R+IPost group (I/R mice treated with IPost); Antagomir-21+IPost+I/R group (I/R mice treated with anagomir-21 and IPost); Scramble+IPost+I/R group (I/R mice treated with scramble and IPost). The results showed IPost could reduce I/R injury-induced infarct size of the left ventricle, improve cardiac function, and prevent myocardial apoptosis, while knockdown of miR-21 with antagomir-21 could reverse these protective effects of IPost against mouse I/R injury. Furthermore, we confirmed that miR-21 plays a protective role in myocardial apoptosis through PTEN/Akt signaling pathway, which was abrogated by the PI3K inhibitor LY294002. The protective effect of miR-21 on myocardial apoptosis was further revealed in mouse hearts after IPost treatment in vivo. Our data clearly demonstrate that miR-21 is involved in IPost-mediated cardiac protection against I/R injury and dysfunction through the PTEN/Akt signaling pathway in vivo. Identifying the beneficial roles of IPost-regulated miRNAs in cardiac protection, which may be a rational target selection for ischemic cardioprotection.Keywords
This publication has 40 references indexed in Scilit:
- CXC-Chemokine Receptor 4 Antagonist AMD3100 Promotes Cardiac Functional Recovery After Ischemia/Reperfusion Injury via Endothelial Nitric Oxide Synthase–Dependent MechanismCirculation, 2013
- Assessing the Global Burden of Ischemic Heart Disease: Part 2: Analytic Methods and Estimates of the Global Epidemiology of Ischemic Heart Disease in 2010CVD Prevention and Control, 2012
- The COX-2/PGI2 Receptor Axis Plays an Obligatory Role in Mediating the Cardioprotection Conferred by the Late Phase of Ischemic PreconditioningPLOS ONE, 2012
- Ischemic postconditioning through percutaneous transluminal coronary angioplasty in pigsCoronary Artery Disease, 2012
- Age, Genetic Characteristics and Number of Cycles Are Critical Factors to Consider for Successful Protection of the Murine Heart With PostconditioningPhysiological Research, 2011
- Effects of ischemic preconditioning on ischemia/reperfusion-induced arrhythmias by upregulatation of connexin 43 expressionJournal of Cardiothoracic Surgery, 2011
- Cardioprotection by ischemic postconditioning is abolished in depressed rats: role of Akt and signal transducer and activator of transcription-3Molecular and Cellular Biochemistry, 2010
- ERK-MAPK Signaling Opposes Rho-Kinase to Reduce Cardiomyocyte Apoptosis in Heart Ischemic PreconditioningMolecular Medicine, 2010
- Ischemic and non-ischemic preconditioning: Endothelium-focused translation into clinical practiceClinical Hemorheology and Microcirculation, 2010
- Evidence for role of epoxyeicosatrienoic acids in mediating ischemic preconditioning and postconditioning in dogAmerican Journal of Physiology-Heart and Circulatory Physiology, 2009