Ischemic postconditioning-mediated miRNA-21 protects against cardiac ischemia/reperfusion injury via PTEN/Akt pathway

• Published in: PloS one 2013-10, Vol.8 (10), p.e75872
• Main Authors: Tu, Yingfeng, Wan, Lin, Fan, Yuhua, Wang, Kezheng, Bu, Lihong, Huang, Tao, Cheng, Zhen, Shen, Baozhong
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Animals; Apoptosis; Apoptosis - drug effects; Apoptosis - genetics; Cardiology; Cardiomyocytes; Cytokines; Enzyme Inhibitors - pharmacology; Gene expression; Gene Expression Regulation - drug effects; Gene Expression Regulation - genetics; Heart; Heart attacks; Heart diseases; Hospitals; Infarction; Injury prevention; Ischemia; Ischemic Postconditioning; Kinases; Laboratory animals; Male; Mice; MicroRNA; MicroRNAs; MicroRNAs - genetics; miRNA; Molecular chains; Molecular modelling; Myocardial infarction; Myocardial ischemia; Myocardial Ischemia - genetics; Myocardial Ischemia - pathology; Myocardial Ischemia - physiopathology; Myocardial Ischemia - therapy; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - pathology; Oligonucleotides - genetics; Ostomy; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - metabolism; PTEN Phosphohydrolase - metabolism; PTEN protein; Reperfusion; Reperfusion Injury - prevention & control; Rodents; Signal transduction; Signal Transduction - drug effects; Signaling; Ventricle; Ventricular Dysfunction, Left - genetics; Ventricular Dysfunction, Left - pathology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0075872

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.