Dorn G W, Brown J H
Department of Medicine, University of Cincinnati College of Medicine, Ohio 45267, USA.
Trends Cardiovasc Med. 1999 Jan-Feb;9(1-2):26-34. doi: 10.1016/s1050-1738(99)00004-3.
Accumulating evidence suggests that cardiac responses to a number of circulating or locally released humoral factors contribute to adaptive responses after hemodynamic stress or myocardial injury. In particular, hormones such as angiotensin II, endothelin 1, norepinephrine and prostaglandin F2 alpha which bind to and activate cardiomyocyte membrane receptors coupled to the Gq class of GTP binding proteins have been implicated in the development and ultimate decompensation of cardiac hypertrophy. Herein we summarize recent developments in cultured cardiomyocyte and transgenic mouse systems which are defining the phenotypes resulting from Gq signaling events in cardiomyocytes, and which are elucidating the critical downstream mediators. Postulated roles for protein kinase C, p38 MAP kinase and jun-N terminal kinase are discussed in relation to Gq-mediated cardiomyocyte hypertrophy and apoptotic signaling. The evidence to date suggests that molecular targeting of Gq or its effectors has the potential to modify cardiac adaptive and maladaptive responses to stress or injury.
越来越多的证据表明，心脏对多种循环或局部释放的体液因子的反应有助于在血流动力学应激或心肌损伤后的适应性反应。特别是，诸如血管紧张素II、内皮素1、去甲肾上腺素和前列腺素F2α等激素，它们与心肌细胞膜受体结合并激活与Gq类GTP结合蛋白偶联的受体，已被认为与心脏肥大的发展和最终失代偿有关。在此，我们总结了培养心肌细胞和转基因小鼠系统的最新进展，这些进展正在确定心肌细胞中Gq信号事件产生的表型，并阐明关键的下游介质。讨论了蛋白激酶C、p38丝裂原活化蛋白激酶和Jun-N末端激酶在Gq介导的心肌细胞肥大和凋亡信号传导中的假定作用。迄今为止的证据表明，对Gq或其效应器进行分子靶向有可能改变心脏对压力或损伤的适应性和适应不良反应。
