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Activated protein C protects against pressure overload-induced hypertrophy through AMPK signaling 期刊论文

编号：

bb55a413-40f0-4c62-982d-fb51e483bed6
作者：

Cates, Courtney#^[1]Rousselle, Thomas#^[1]Wang, Jinli#^[2]Quan, Nanhu(全南虎)^[1,3]Wang, Lin(王琳)^[1,3]Chen, Xu^[4];Yang, Likui^[5];Rezaie, Alireza R.*^[5]Li, Ji*^[1]
语种：

English
期刊：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS ISSN：0006-291X 2018 年 495 卷 4 期 (2584 - 2594) ; JAN 22
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关键词：

APC PAR1 Cytoprotective AMPK Hypertrophy
摘要：

We found that the anticoagulant plasma protease, activated protein C (APC), stimulates the energy sensor kinase, AMPK, in the stressed heart by activating protease-activated receptor 1 (PAR1) on cardiomyocytes. Wild-type (WT) and AMPK-kinase dead (KD) transgenic mice were subjected to transverse aortic constriction (TAC) surgery. The results demonstrated that while no phenotypic differences can be observed between WT and AMPK-KD mice under normal physiological conditions, AMPK-KD mice exhibit significantly larger hearts after 4 weeks of TAC surgery. Analysis by echocardiography suggested that the impairment in the cardiac function of AMPK-KD hearts is significantly greater than that of WT hearts. Immunohistochemical staining revealed increased macrophage infiltration and ROS generation in AMPK-KD hearts after 4 weeks of TAC surgery. Immunoblotting results demonstrated that the redox markers, pShc(66), 4-hydroxynonenal and ERK, were all up-regulated at a higher extent in AMPK-KD hearts after 4 weeks of TAC surgery. Administration of APC-WT and the signaling selective APC-2Cys mutant, but not the anticoagulant selective APC-E170A mutant, significantly attenuated pressure overload-induced hypertrophy and fibrosis. Macrophage infiltration and pShc(66) activation caused by pressure overload were also inhibited by APC and APC-2Cys but not by APC-E170A. Therefore, the cardiac AMPK protects against pressure overload-induced hypertrophy and the signaling selective APC-2Cys may have therapeutic potential for treating hypertension-related hypertrophy without increasing the risk of bleeding. (C) 2017 Elsevier Inc. All rights reserved.
推荐引用方式
GB/T 7714：

Cates Courtney,Rousselle Thomas,Wang Jinli, et al. Activated protein C protects against pressure overload-induced hypertrophy through AMPK signaling [J].BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2018,495(4):2584-2594.
APA：

Cates Courtney,Rousselle Thomas,Wang Jinli,Quan Nanhu,&Li Ji.(2018).Activated protein C protects against pressure overload-induced hypertrophy through AMPK signaling .BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,495(4):2584-2594.
MLA：

Cates Courtney, et al. "Activated protein C protects against pressure overload-induced hypertrophy through AMPK signaling" .BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 495,4(2018):2584-2594.
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