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Rap1 promotes endothelial mechanosensing complex formation, NO release and normal endothelial function.

ABSTRACT: Decreased nitric oxide (NO) bioavailability underlies a number of cardiovascular pathologies, including hypertension. The shear stress exerted by flowing blood is the main determinant of NO release. Rap1 promotes integrin- and cadherin-mediated signaling. Here, we show that Rap1 is a critical regulator of NO production and endothelial function. Rap1 deficiency in murine endothelium attenuates NO production and diminishes NO-dependent vasodilation, leading to endothelial dysfunction and hypertension, without deleterious effects on vessel integrity. Mechanistically, Rap1 is activated by shear stress, promotes the formation of the endothelial mechanosensing complex-comprised of PECAM-1, VE-cadherin and VEGFR2- and downstream signaling to NO production. Our study establishes a novel paradigm for Rap1 as a regulator of mechanotransduction.

SUBMITTER: Lakshmikanthan S

PROVIDER: S-EPMC4428051 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Rap1 promotes endothelial mechanosensing complex formation, NO release and normal endothelial function.

Lakshmikanthan Sribalaji S Zheng Xiaodong X Nishijima Yoshinori Y Sobczak Magdalena M Szabo Aniko A Vasquez-Vivar Jeannette J Zhang David X DX Chrzanowska-Wodnicka Magdalena M

EMBO reports 20150325 5

Decreased nitric oxide (NO) bioavailability underlies a number of cardiovascular pathologies, including hypertension. The shear stress exerted by flowing blood is the main determinant of NO release. Rap1 promotes integrin- and cadherin-mediated signaling. Here, we show that Rap1 is a critical regulator of NO production and endothelial function. Rap1 deficiency in murine endothelium attenuates NO production and diminishes NO-dependent vasodilation, leading to endothelial dysfunction and hypertens ...[more]

PMID: 25807985

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