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Rap1 promotes endothelial mechanosensing complex formation, NO release and normal endothelial function. EMBO Rep 2015 May;16(5):628-37

Date

03/27/2015

Pubmed ID

25807985

Pubmed Central ID

PMC4428051

DOI

10.15252/embr.201439846

Scopus ID

2-s2.0-84928885238 (requires institutional sign-in at Scopus site)   42 Citations

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.

Author List

Lakshmikanthan S, Zheng X, Nishijima Y, Sobczak M, Szabo A, Vasquez-Vivar J, Zhang DX, Chrzanowska-Wodnicka M

Authors

Magdalena Chrzanowska PhD Associate Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Aniko Szabo PhD Professor in the Data Science Institute department at Medical College of Wisconsin
Jeannette M. Vasquez-Vivar PhD Professor in the Biophysics department at Medical College of Wisconsin
David X. Zhang MD, PhD Associate Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Blood Pressure
Capillary Permeability
Endothelium
Humans
Hypertension
Hypertrophy, Left Ventricular
Male
Mechanotransduction, Cellular
Mice
Mice, Knockout
Models, Biological
Nitric Oxide
Nitric Oxide Synthase Type III
Organ Specificity
Signal Transduction
Vasodilation
rap1 GTP-Binding Proteins