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

  • Lakshmikanthan S
  • Zheng X
  • Nishijima Y
 et al. 
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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-supplied keywords

  • 15252
  • 201439846
  • angiogenesis
  • doi 10
  • embr
  • mechanotransduction
  • nitric oxide
  • rap 1
  • received 7 november 2014
  • revised 28
  • shear stress
  • small gtpase
  • subject categories signal transduction
  • vascular biology
  • vasodilation

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Authors

  • Sribalaji Lakshmikanthan

  • Xiaodong Zheng

  • Yoshinori Nishijima

  • Magdalena Sobczak

  • Aniko Szabo

  • Jeannette Vasquez-Vivar

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