The protective effect of trimetazidine on myocardial ischemia/reperfusion injury through activating AMPK and ERK signaling pathway
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- 英文论文题名：The protective effect of trimetazidine on myocardial ischemia/reperfusion injury through activating AMPK and ERK signaling pathway
- 论文作者：Zhu Ping ; Liu Zhenling ; Chen Ji-Mei ; Huang Huanlei ; Kuznicki Michelle ; Zheng Shaoyi ; Sun Wanqing ; Quan Nanhu ; Wang Lin ; Yang Hui ; Guo Hui-Ming ; Li Ji ; Zhuang Jian
- 英文论文作者：Zhu Ping ; Liu Zhenling ; Chen Ji-Mei ; Huang Huanlei ; Kuznicki Michelle ; Zheng Shaoyi ; Sun Wanqing ; Quan Nanhu ; Wang Lin ; Yang Hui ; Guo Hui-Ming ; Li Ji ; Zhuang Jian ; Guangdong Cardiovascular Institute ; Guangdong General Hospital ; Guangdong Academy of Medical Sciences ; State University of New York at Buffalo ; Department of Physiology and Biophysics ; University of Mississippi Medical Center
- 年：2016
- 作者机构：Guangdong Cardiovascular Institute,Guangdong General Hospital,Guangdong Academy of Medical Sciences;State University of New York at Buffalo;Department of Physiology and Biophysics,University of Mississippi Medical Center;
- 英文论文关键词：AMPK signaling ; APK signaling ; Trimetazidine ; Cardioprotection ; Ischemia/reperfusion
- 会议召开时间：2016-11-04
- 会议录名称：第十一届全国免疫学学术大会摘要汇编
- 英文会议录名称：Abstracts of 2016 CSI Congress on Immunology
- 语种：英文
- 分类号：R542.22
- 学会代码：IGMD
- 会议名称：第十一届全国免疫学学术大会
- 会议地点：中国安徽合肥
- 主办单位：中国免疫学会
- 学会名称：中国免疫学会
- 页数：1
- 文件大小：341k
- 原文格式：D
- 会议级别：全国
摘要
Objectives: Trimetazidine(TMZ) can optimize energy metabolism via inhibition of long-chain 3-ketoacyl Co A thiolase(3-KAT) in the heart, with subsequent decrease in fatty acid oxidation and stimulation of glucose oxidation. TMZ changes the cardiac AMP/ATP ratio by modulating fatty acid oxidation, thereby triggering AMPK signaling cascade that contributes to the protection of the heart from ischemia/reperfusion(I/R) injury. Methods: The mouse model of in vivo regional ischemia and reperfusion by the ligation of the left anterior descending coronary artery(LAD) was used for determination of myocardial infarction. The infarct size was compared between C57BL/6J WT mice and AMPK kinase dead(KD) transgenic mice with or without TMZ treatment. The ex vivo working heart perfusion system was used to monitor the effect of TMZ on glucose oxidation and fatty acid oxidation in the heart. Results: TMZ treatment significantly stimulates cardiac AMPK and extracellular signal regulated kinase(ERK) signaling pathways(p < 0.05 vs. vehicle group). The ex vivo working heart perfusion data demonstrated that TMZ treatment significantly activates AMPK signaling and modulating the substrate metabolism by shifting fatty acid oxidation to glucose oxidation during reperfusion, leading to reduction of oxidative stress in the I/R hearts. Therefore, both AMPK and ERK signaling pathways mediate the cardioprotection of TMZ against ischemic injury. Conclusion: We demonstrate that trimetazidine regulate metabolism during myocardial ischemia/reperfusion injury through regulating AMPK signaling pathway, and trimetazidine can reduce myocardial infarction size through AMPK and ERK signaling pathways. The result that AMPK KD mice or AMPK inhibitor compound C, ERK inhibitor PD98059 abolished the cardioprotective effect of trimetazidine further confirmed the hypothesis that trimetazidine exerts its protective effect through activating AMPK signaling pathway as well as trimetazidine's protective effect through regulating ERK signaling pathway.
Objectives: Trimetazidine(TMZ) can optimize energy metabolism via inhibition of long-chain 3-ketoacyl Co A thiolase(3-KAT) in the heart, with subsequent decrease in fatty acid oxidation and stimulation of glucose oxidation. TMZ changes the cardiac AMP/ATP ratio by modulating fatty acid oxidation, thereby triggering AMPK signaling cascade that contributes to the protection of the heart from ischemia/reperfusion(I/R) injury. Methods: The mouse model of in vivo regional ischemia and reperfusion by the ligation of the left anterior descending coronary artery(LAD) was used for determination of myocardial infarction. The infarct size was compared between C57BL/6J WT mice and AMPK kinase dead(KD) transgenic mice with or without TMZ treatment. The ex vivo working heart perfusion system was used to monitor the effect of TMZ on glucose oxidation and fatty acid oxidation in the heart. Results: TMZ treatment significantly stimulates cardiac AMPK and extracellular signal regulated kinase(ERK) signaling pathways(p < 0.05 vs. vehicle group). The ex vivo working heart perfusion data demonstrated that TMZ treatment significantly activates AMPK signaling and modulating the substrate metabolism by shifting fatty acid oxidation to glucose oxidation during reperfusion, leading to reduction of oxidative stress in the I/R hearts. Therefore, both AMPK and ERK signaling pathways mediate the cardioprotection of TMZ against ischemic injury. Conclusion: We demonstrate that trimetazidine regulate metabolism during myocardial ischemia/reperfusion injury through regulating AMPK signaling pathway, and trimetazidine can reduce myocardial infarction size through AMPK and ERK signaling pathways. The result that AMPK KD mice or AMPK inhibitor compound C, ERK inhibitor PD98059 abolished the cardioprotective effect of trimetazidine further confirmed the hypothesis that trimetazidine exerts its protective effect through activating AMPK signaling pathway as well as trimetazidine's protective effect through regulating ERK signaling pathway.
Objectives: Trimetazidine(TMZ) can optimize energy metabolism via inhibition of long-chain 3-ketoacyl Co A thiolase(3-KAT) in the heart, with subsequent decrease in fatty acid oxidation and stimulation of glucose oxidation. TMZ changes the cardiac AMP/ATP ratio by modulating fatty acid oxidation, thereby triggering AMPK signaling cascade that contributes to the protection of the heart from ischemia/reperfusion(I/R) injury. Methods: The mouse model of in vivo regional ischemia and reperfusion by the ligation of the left anterior descending coronary artery(LAD) was used for determination of myocardial infarction. The infarct size was compared between C57BL/6J WT mice and AMPK kinase dead(KD) transgenic mice with or without TMZ treatment. The ex vivo working heart perfusion system was used to monitor the effect of TMZ on glucose oxidation and fatty acid oxidation in the heart. Results: TMZ treatment significantly stimulates cardiac AMPK and extracellular signal regulated kinase(ERK) signaling pathways(p < 0.05 vs. vehicle group). The ex vivo working heart perfusion data demonstrated that TMZ treatment significantly activates AMPK signaling and modulating the substrate metabolism by shifting fatty acid oxidation to glucose oxidation during reperfusion, leading to reduction of oxidative stress in the I/R hearts. Therefore, both AMPK and ERK signaling pathways mediate the cardioprotection of TMZ against ischemic injury. Conclusion: We demonstrate that trimetazidine regulate metabolism during myocardial ischemia/reperfusion injury through regulating AMPK signaling pathway, and trimetazidine can reduce myocardial infarction size through AMPK and ERK signaling pathways. The result that AMPK KD mice or AMPK inhibitor compound C, ERK inhibitor PD98059 abolished the cardioprotective effect of trimetazidine further confirmed the hypothesis that trimetazidine exerts its protective effect through activating AMPK signaling pathway as well as trimetazidine's protective effect through regulating ERK signaling pathway.
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