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




Autophagy Is Involved in the Cardioprotection Effect of Remote Limb Ischemic Postconditioning on Myocardial Ischemia-Reperfusion Injury in Normal Mice, but Not Diabetic Mice - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

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.



Autor: Zhihua Han , Jiatian Cao , Dongqiang Song , Lei Tian, Kan Chen, Yue Wang, Lin Gao, Zhaofang Yin, Yuqi Fan , Changqian Wang

Fuente: http://plos.srce.hr/



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