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


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.
Department of Cardiology, Ninth People's Hospital, Shanghai Jiaotong University Medical School, PR China.
Zhihua
Z
Han
Department of Cardiology, Ninth People's Hospital, Shanghai Jiaotong University Medical School, PR China.
Jiatian
J
Cao
Department of Cardiology, Ninth People's Hospital, Shanghai Jiaotong University Medical School, PR China.
Dongqiang
D
Song
Department of Cardiology, Ninth People's Hospital, Shanghai Jiaotong University Medical School, PR China.
Lei
L
Tian
Department of Cardiology, Ninth People's Hospital, Shanghai Jiaotong University Medical School, PR China.
Kan
K
Chen
Department of Cardiology, Ninth People's Hospital, Shanghai Jiaotong University Medical School, PR China.
Yue
Y
Wang
Department of Cardiology, Ninth People's Hospital, Shanghai Jiaotong University Medical School, PR China.
Lin
L
Gao
Department of Cardiology, Ninth People's Hospital, Shanghai Jiaotong University Medical School, PR China.
Zhaofang
Z
Yin
Department of Cardiology, Ninth People's Hospital, Shanghai Jiaotong University Medical School, PR China.
Yuqi
Y
Fan
Department of Cardiology, Ninth People's Hospital, Shanghai Jiaotong University Medical School, PR China.
Changqian
C
Wang
D000818:Animals; D001343:Autophagy; D015153:Blotting, Western; D002316:Cardiotonic Agents; D003921:Diabetes Mellitus, Experimental / Q000401:mortality / Q000473:pathology*; D004195:Disease Models, Animal; D004452:Echocardiography; D006614:Hindlimb / Q000098:blood supply*; D007124:Immunoenzyme Techniques; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015428:Myocardial Reperfusion Injury / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D015996:Survival Rate
D002316:Cardiotonic Agents