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Endothelial nitric oxide synthase inhibits G12/13 and rho-kinase activated by the angiotensin II type-1 receptor: implication in vascular migration.


ABSTRACT: Although, endothelial nitric oxide (NO) synthase (eNOS) is believed to antagonize vascular remodeling induced by the angiotensin II (AngII) type-1 receptor, the exact signaling mechanism remains unclear.By expressing eNOS to vascular smooth muscle cells (VSMCs) via adenovirus, we investigated a signal transduction mechanism of the eNOS gene transfer in preventing vascular remodeling induced by AngII. We found marked inhibition of AngII-induced Rho/Rho-kinase activation and subsequent VSMC migration by eNOS gene transfer whereas G(q)-dependent transactivation of the epidermal growth factor receptor by AngII remains intact. This could be explained by the specific inhibition of G(12/13) activation by eNOS-mediated G(12/13) phosphorylation.The eNOS/NO cascade specifically targets the Rho/Rho-kinase system via inhibition of G(12/13) to prevent vascular migration induced by AngII, representing a novel signal cross-talk in cardiovascular protection by NO.

SUBMITTER: Suzuki H 

PROVIDER: S-EPMC2704976 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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Endothelial nitric oxide synthase inhibits G12/13 and rho-kinase activated by the angiotensin II type-1 receptor: implication in vascular migration.

Suzuki Hiroyuki H   Kimura Keita K   Shirai Heigoro H   Eguchi Kunie K   Higuchi Sadaharu S   Hinoki Akinari A   Ishimaru Kazuhiro K   Brailoiu Eugen E   Dhanasekaran Danny N DN   Stemmle Laura N LN   Fields Timothy A TA   Frank Gerald D GD   Autieri Michael V MV   Eguchi Satoru S  

Arteriosclerosis, thrombosis, and vascular biology 20081218 2


<h4>Background</h4>Although, endothelial nitric oxide (NO) synthase (eNOS) is believed to antagonize vascular remodeling induced by the angiotensin II (AngII) type-1 receptor, the exact signaling mechanism remains unclear.<h4>Methods and results</h4>By expressing eNOS to vascular smooth muscle cells (VSMCs) via adenovirus, we investigated a signal transduction mechanism of the eNOS gene transfer in preventing vascular remodeling induced by AngII. We found marked inhibition of AngII-induced Rho/R  ...[more]

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