Revisited and revised: is RhoA always a villain in cardiac pathophysiology?
Revisited and revised: is RhoA always a villain in cardiac pathophysiology?
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DOI：
10.1007/s12265-010-9192-8
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发表时间：
2010-08
影响因子：
3.4
通讯作者：
Brown, Joan Heller
中科院分区：
文献类型：
--
作者：
Miyamoto, Shigeki;Del Re, Dominic P.;Xiang, Sunny Y.;Zhao, Xia;Florholmen, Geir;Brown, Joan Heller
新生大鼠心室肌细胞肥大模型提供了关于调节心脏生长和基因表达的信号通路的巨大见解。因此发现的许多介质已成功地外推到体内环境中，如使用基因工程小鼠和生理干预所评估的。对新生大鼠心室肌细胞的研究表明，小G蛋白RhoA及其下游效应激酶Rho相关卷曲螺旋蛋白激酶（ROCK）在激动剂介导的肥大中发挥作用。然而，RhoA在心脏中的转基因表达并不能表型复制这种反应，ROCK的基因缺失也不能防止肥大。ROCK的药理学抑制具有与RhoA信号传导在心力衰竭的发展或对缺血性损伤的反应中的作用最一致的作用。然而，RhoA下游引发的信号是否促进细胞死亡或存活以及是有害的还是有益的，是背景和细胞类型依赖的。本文综述了上述概念，并提出了RhoA可能保护心肌细胞免受缺血和其他损伤的假设。新型RhoA靶点包括磷脂调节和调节酶（Akt、PI激酶、磷脂酶C、蛋白激酶C和D）和血清反应元件介导的转录反应被认为是RhoA影响心肌细胞存活的可能途径。
The neonatal rat ventricular myocyte model of hypertrophy has provided tremendous insight with regard to signaling pathways regulating cardiac growth and gene expression. Many mediators thus discovered have been successfully extrapolated to the in vivo setting, as assessed using genetically engineered mice and physiological interventions. Studies in neonatal rat ventricular myocytes demonstrated a role for the small G-protein RhoA and its downstream effector kinase, Rho-associated coiled-coil containing protein kinase (ROCK), in agonist-mediated hypertrophy. Transgenic expression of RhoA in the heart does not phenocopy this response, however, nor does genetic deletion of ROCK prevent hypertrophy. Pharmacologic inhibition of ROCK has effects most consistent with roles for RhoA signaling in the development of heart failure or responses to ischemic damage. Whether signals elicited downstream of RhoA promote cell death or survival and are deleterious or salutary is, however, context and cell-type dependent. The concepts discussed above are reviewed, and the hypothesis that RhoA might protect cardiomyocytes from ischemia and other insults is presented. Novel RhoA targets including phospholipid regulated and regulating enzymes (Akt, PI kinases, phospholipase C, protein kinases C and D) and serum response element-mediated transcriptional responses are considered as possible pathways through which RhoA could affect cardiomyocyte survival.
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影响因子：
3.9
作者：
Asemu, G;Dent, MR;Tappia, PS
通讯作者：
Tappia, PS
DOI：
10.1073/pnas.191369098
发表时间：
2001-09-25
影响因子：
11.1
作者：
Chen, L;Hahn, H;Mochly-Rosen, D
通讯作者：
Mochly-Rosen, D
影响因子：
4
作者：
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通讯作者：
Prywes, R
影响因子：
64.8
作者：
Bence, K;Ma, W;Huang, XY
通讯作者：
Huang, XY
影响因子：
10.8
作者：
Bao, WK;Hu, E;Yue, TL
通讯作者：
Yue, TL