Novel aspects of the roles of Rac1 GTPase in the cardiovascular system - PubMed (original) (raw)

Review

Novel aspects of the roles of Rac1 GTPase in the cardiovascular system

Naoki Sawada et al. Curr Opin Pharmacol. 2010 Apr.

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.

Keywords: NADPH oxidase; ROS; Rac1; actin cytoskeleton; angiogenesis; atrial fibrillation; cardiac hypertrophy; eNOS; endothelium-derived neurotrophic activity; heart failure.

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Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

Figure 1

Proposed model of neuroprotection through targeting endothelial Rac1. BM: Basement membrane; EC: endothelial cell; ECM: Extracellular matrix; HSP: Heat shock protein; ROS: Reactive oxygen species. Adapted with permission from the reference [9].

Figure 2

Context-dependent, Janus-faced functions of Rac1 in endothelial cell signaling. Different signaling axes encompassing distinct sets of upstream stimuli, GEF, Rac1 and effector(s) exert opposite effects on endothelial function, angiogenesis, EC survival (A), and endothelial barrier function (B).

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Novel aspects of the roles of Rac1 GTPase in the cardiovascular system - PubMed (original) (raw)