Rac1 GTP 酶在心血管系统中作用的新方面。
Novel aspects of the roles of Rac1 GTPase in the cardiovascular system.
机构信息
Global Center of Excellence Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, 24th Floor, Research Building II, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
出版信息
Curr Opin Pharmacol. 2010 Apr;10(2):116-21. doi: 10.1016/j.coph.2009.11.004. Epub 2010 Jan 7.
Abstract
Rac1 GTPase is an established master regulator of cell motility through cortical actin re-organization and of reactive oxygen species generation through regulation of NADPH oxidase activity. Numerous molecular and cellular studies have implicated Rac1 in various cardiovascular pathologies: vascular smooth muscle proliferation, cardiomyocyte hypertrophy, and endothelial cell shape change. The physiological relevance of these in vitro findings, however, is just beginning to be reassessed with the newly developed, conditional mouse mutagenesis technology. Conditional gene targeting has also revealed unexpected, cell type-specific roles of Rac1. The aim of this review is to summarize the recent advance made in Rac1 research in the cardiovascular system, with special focus on its novel roles in the regulation of endothelial function, angiogenesis, and endothelium-mediated neuroprotection.
摘要
Rac1 GTPase 通过皮层肌动蛋白的重新组织调节细胞运动，通过调节 NADPH 氧化酶的活性调节活性氧的产生，是细胞运动的既定主调控因子。大量的分子和细胞研究表明 Rac1 参与了多种心血管疾病：血管平滑肌增殖、心肌细胞肥大和内皮细胞形态改变。然而，随着新开发的条件性小鼠诱变技术的出现，这些体外发现的生理相关性才刚刚开始重新评估。条件性基因靶向也揭示了 Rac1 在细胞类型特异性方面的意外作用。本文综述了心血管系统中 Rac1 研究的最新进展，特别关注其在调节内皮功能、血管生成和内皮介导的神经保护中的新作用。
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