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学科主题临床医学
Activation of alpha(1B)-adrenoceptors contributes to intermittent hypobaric hypoxia-improved postischemic myocardial performance via inhibiting MMP-2 activation
Gao, Ling1,2; Chen, Le1,2; Lu, Zhi-Zhen3,4; Gao, Hong1,2; Wu, Lan1,2; Chen, Yi-Xiong1,2; Zhang, Cai-Mei1,2; Jiang, Yu-Kun1,2; Jing, Qing1,2; Zhang, You-Yi3,4; Yang, Huang-Tian1,2
关键词Intermittent Hypobaric Hypoxia Ischemia-reperfusion Injury Matrix Metalloenzymes-2 Alpha(1)-adrenoceptors Mitochondria
刊名AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
2014-06-01
DOI10.1152/ajpheart.00772.2013
306期:11页:H1569-H1581
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cardiac & Cardiovascular Systems ; Physiology ; Peripheral Vascular Disease
研究领域[WOS]Cardiovascular System & Cardiology ; Physiology
关键词[WOS]ISCHEMIA-REPERFUSION INJURY ; HIGH-ALTITUDE HYPOXIA ; PROTEIN-KINASE-C ; MATRIX METALLOPROTEINASE-2 ACTIVITY ; CA2+ OVERLOAD INJURY ; RAT HEARTS ; ISCHEMIA/REPERFUSION INJURY ; ALPHA(1)-ADRENERGIC RECEPTOR ; INDUCED CARDIOPROTECTION ; TISSUE INHIBITOR
英文摘要

Inhibition of matrix metalloproteinases-2 (MMP-2) activation renders cardioprotection from ischemia/reperfusion (I/R) injury; however, the signaling pathways involved have not been fully understood. Intermittent hypobaric hypoxia (IHH) has been shown to enhance myocardial tolerance to I/R injury via triggering intrinsic adaptive responses. Here we investigated whether IHH protects the heart against I/R injury via the regulation of MMP-2 and how the MMP-2 is regulated. IHH (PO2 = 84 mmHg, 4-h/day, 4 wk) improved postischemic myocardial contractile performance, lactate dehydrogenase (LDH) release, and infarct size in isolated perfused rat hearts. Moreover, IHH reversed I/R-induced MMP-2 activation and release, disorders in the levels of MMP-2 regulators, peroxynitrite (ONOO-) and tissue inhibitor of metalloproteinase-4 (TIMP-4), and loss of the MMP-2 targets alpha-actinin and troponin I. This protection was mimicked, but not augmented, by a MMP inhibitor doxycycline and lost by the alpha(1)-adrenoceptor (AR) antagonist prazosin. Furthermore, IHH increased myocardial alpha(1A)-AR and alpha(1B)-AR density but not alpha(1D)-AR after I/R. Concomitantly, IHH further enhanced the translocation of PKC epsilon (PKC epsilon) and decreased the release of mitochondrial cytochrome c due to I/R via the activation of alpha(1B)-AR but not alpha(1A)-AR or alpha(1D)-AR. IHH-conferred cardioprotection in the postischemic contractile function, LDH release, MMP-2 activation, and nitrotyrosine as well as TIMP-4 contents were mimicked but not additive by alpha(1)-AR stimulation with phenylephrine and were abolished by an alpha(1B)-AR antagonist chloroethylclonidine and a PKC epsilon inhibitor PKC epsilon V1-2. These findings demonstrate that IHH exerts cardioprotection through attenuating excess ONOO- biosynthesis and TIMP-4 loss and sequential MMP-2 activation via the activation of alpha(1B)-AR/PKC epsilon pathway.

语种英语
WOS记录号WOS:000337235300009
引用统计
被引频次:8[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/53422
专题北京大学第三临床医学院_心血管内科
北京大学口腔医学院_麻醉科
作者单位1.Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Key Lab Stem Cell Biol, Shanghai, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Mol Cardiol Lab, Shanghai, Peoples R China
4.Peking Univ, Hosp 3, Inst Vasc Med, Beijing 100871, Peoples R China
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GB/T 7714
Gao, Ling,Chen, Le,Lu, Zhi-Zhen,et al. Activation of alpha(1B)-adrenoceptors contributes to intermittent hypobaric hypoxia-improved postischemic myocardial performance via inhibiting MMP-2 activation[J]. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY,2014,306(11):H1569-H1581.
APA Gao, Ling.,Chen, Le.,Lu, Zhi-Zhen.,Gao, Hong.,Wu, Lan.,...&Yang, Huang-Tian.(2014).Activation of alpha(1B)-adrenoceptors contributes to intermittent hypobaric hypoxia-improved postischemic myocardial performance via inhibiting MMP-2 activation.AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY,306(11),H1569-H1581.
MLA Gao, Ling,et al."Activation of alpha(1B)-adrenoceptors contributes to intermittent hypobaric hypoxia-improved postischemic myocardial performance via inhibiting MMP-2 activation".AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY 306.11(2014):H1569-H1581.
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