Hyperlipidemia does not prevent the cardioprotection by postconditioning against myocardial ischemia/reperfusion injury and the involvement of hypoxia inducible factor-1α upregulation  

作　　者：Huanxin Zhao Yehong Wang Ye Wu Xiaoyu Li Guangzhao Yang Xiurui Ma Rongmi Zhao Huirong Liu 

机构地区：[1]Department of Physiology, Shanxi Medical University, Taiyuan 030001, China [2]Key Laboratory of Cellular Physiology, Shanxi Medical University, Chinese Education Ministry, Taiyuan 030001, China [3]School of Basic Medical Sciences, and Cardiovascular Research Institute, Capital Medical University, Beijing 100069, China [4]Shanxi College of Traditional Chinese Medicine, Taiyuan 030012, China

出　　处：《Acta Biochimica et Biophysica Sinica》2009年第9期745-753,共9页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the grants from the National Natural Science Foundation （No. 30572084 and 30700276） and Undergraduation Technological Innovation of Taiyuan City （08122085 to Huanxin Zhao）.

摘　　要：Hyperlipidemia is regarded as an independent risk factor in the development of ischemic heart disease, and it can increase the myocardial susceptibility to ischemia/reperfusion （I/R） injury, lschemic postconditioning （Postcon） has been demonstrated to attenuate the myocardial injury induced by I/R in normal conditions. But the effect of ischemic Postcon on hyperlipidemic animals is unknown. Hypoxia inducible factor-1 （HIF-1） has been demonstrated to play a central role in the cardioprotection by preconditioning, which is one of the protective strategies except for Postcon. The aim of this study was to determine whether Postcon could reduce myocardial injury in hyperlipidemic animals and to assess whether HIF-1 was involved in Postcon mechanisms. Male Wistar rats underwent the left anterior descending coronary occlusion for 30 min followed by 180min of reperfusion with or without Postcon after fed with high fat diet or normal diet for 8 weeks. The detrimental indices induced by the I/R insult included infarct size, plasma creatine kinase activity and caspase-3 activity. Results showed that hyperlipidemia remarkably enhanced the myocardial injury induced by I/R, while Postcon significantly decreased the myocardial injury in both normolipidemie and hyperlipidemic rats. Moreover, both hyperlipidemia and I/R promoted the HIF-αL expression. Most importantly, we have for the first time demonstrated that Postcon further induced a significant increase in HIF-αL protein level not only in normolipidemie but also in hyperlipidemic conditions. Thus, Postcon reduces the myocardial injury induced by I/R in normal and hyperlipidemic animals, and HIF-αL upregulation may involve in the Postcon-mediated cardioprotective mechanisms.Hyperlipidemia is regarded as an independent risk factor in the development of ischemic heart disease, and it can increase the myocardial susceptibility to ischemia/reperfusion （I/R） injury, lschemic postconditioning （Postcon） has been demonstrated to attenuate the myocardial injury induced by I/R in normal conditions. But the effect of ischemic Postcon on hyperlipidemic animals is unknown. Hypoxia inducible factor-1 （HIF-1） has been demonstrated to play a central role in the cardioprotection by preconditioning, which is one of the protective strategies except for Postcon. The aim of this study was to determine whether Postcon could reduce myocardial injury in hyperlipidemic animals and to assess whether HIF-1 was involved in Postcon mechanisms. Male Wistar rats underwent the left anterior descending coronary occlusion for 30 min followed by 180min of reperfusion with or without Postcon after fed with high fat diet or normal diet for 8 weeks. The detrimental indices induced by the I/R insult included infarct size, plasma creatine kinase activity and caspase-3 activity. Results showed that hyperlipidemia remarkably enhanced the myocardial injury induced by I/R, while Postcon significantly decreased the myocardial injury in both normolipidemie and hyperlipidemic rats. Moreover, both hyperlipidemia and I/R promoted the HIF-αL expression. Most importantly, we have for the first time demonstrated that Postcon further induced a significant increase in HIF-αL protein level not only in normolipidemie but also in hyperlipidemic conditions. Thus, Postcon reduces the myocardial injury induced by I/R in normal and hyperlipidemic animals, and HIF-αL upregulation may involve in the Postcon-mediated cardioprotective mechanisms.

关 键 词：HYPERLIPIDEMIA ischemic postconditioning myocardial infarction hypoxia inducible factor-1 

分 类 号：Q959.802[生物学—动物学] S852.2[农业科学—基础兽医学]