Autophagy Is Involved in the Cardioprotection Effect of Remote Limb Ischemic Postconditioning on Myocardial Ischemia/Reperfusion Injury in Normal Mice, but Not Diabetic Mice

• Published in: PloS one Vol. 9; no. 1; p. e86838
• Main Authors: Han, Zhihua, Cao, Jiatian, Song, Dongqiang, Tian, Lei, Chen, Kan, Wang, Yue, Gao, Lin, Yin, Zhaofang, Fan, Yuqi, Wang, Changqian
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23.01.2014; Public Library of Science (PLoS)
• Subjects: Analysis; Animals; Autophagy; Biology; Blotting, Western; Cardiology; Cardiotonic Agents; Cell death; Clinical trials; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - mortality; Diabetes Mellitus, Experimental - pathology; Disease Models, Animal; Echocardiography; Glucose; Heart attacks; Heart diseases; Hindlimb - blood supply; Hospitals; Immunoenzyme Techniques; Immunohistochemistry; Injuries; Ischemia; Ischemic Preconditioning, Myocardial; Kinases; Laboratory animals; Male; Medical research; Medical schools; Medicine; Mice; Mice, Inbred C57BL; Mortality; Myocardial ischemia; Myocardial Reperfusion Injury - mortality; Myocardial Reperfusion Injury - pathology; Myocardial Reperfusion Injury - prevention & control; Myocardium; Phagocytosis; Proteins; Reperfusion; Rodents; Streptozocin; Survival Rate; Veins & arteries; Veterinary Science; China
• DOI: 10.1371/journal.pone.0086838
• ISSN: 1932-6203

Recent animal study and clinical trial data suggested that remote limb ischemic postconditioning (RIPostC) can invoke potent cardioprotection. However, during ischemia reperfusion injury (IR), the effect and mechanism of RIPostC on myocardium in subjects with or without diabetes mellitus (DM) are poorly understood. Autophagy plays a crucial role in alleviating myocardial IR injury. The aim of this study was to determine the effect of RIPostC on mice myocardial IR injury model with or without DM, and investigate the role of autophagy in this process. Streptozocin (STZ) induced DM mice model and myocardial IR model were established. Using a noninvasive technique, RIPostC was induced in normal mice (ND) and DM mice by three cycles of ischemia (5 min) and reperfusion (5 min) in the left hindlimb. In ND group, RIPostC significantly reduced infarct size (32.6±3.0% in ND-RIPostC vs. 50.6±2.4% in ND-IR, p<0.05) and improved cardiac ejection fraction (49.70±3.46% in ND-RIPostC vs. 31.30±3.95% in ND-IR, p<0.05). However, in DM group, no RIPostC mediated cardioprotetion effect was observed. To analyze the role of autophagy, western blot and immunohistochemistry was performed. Our data showed that a decreased sequestosome 1 (SQSTM1/p62) level, an increased Beclin-1 level, and higher ratio of LC3-II/LC3-I were observed in ND RIPostC group, but not DM RIPostC group. The current study suggested that RIPostC exerts cardioprotection effect on IR in normal mice, but not DM mice, and this difference is via, at least in part, the up-regulation of autophagy.