Autophagy is involved in the cardioprotection effect of remote limb ischemic postconditioning on myocardial ischemia/reperfusion injury in normal mice, but not diabetic mice

PLoS One. 2014 Jan 23;9(1):e86838. doi: 10.1371/journal.pone.0086838. eCollection 2014.

Abstract

Background: 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.

Methodology and results: 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.

Conclusions: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy*
  • Blotting, Western
  • Cardiotonic Agents*
  • Diabetes Mellitus, Experimental / mortality
  • Diabetes Mellitus, Experimental / pathology*
  • Disease Models, Animal*
  • Echocardiography
  • Hindlimb / blood supply*
  • Immunoenzyme Techniques
  • Ischemic Preconditioning, Myocardial*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myocardial Reperfusion Injury / mortality
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / prevention & control*
  • Survival Rate

Substances

  • Cardiotonic Agents

Grants and funding

This work was supported by the Chinese National Natural Science Foundation Grants (Grant No. 81270376 and 31201010), project supported by the Shanghai Committee of Science and Technology of China (Grant No. 12ZR1419500, 114119a8700), Shanghai’s health bureau funding (Grant No. ZYSNXD-CC-ZDYJ029) and Doctoral students innovation fund of Shanghai Jiaotong University School of Medicine (BXJ201229, BXJ201228). Research Fund for the Doctoral Program of Higher Education of China (20130072110016). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.