Rap1 promotes endothelial mechanosensing complex formation, NO release and normal endothelial function
Copyright policy )Rap1 promotes endothelial mechanosensing complex formation, NO release and normal endothelial function
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.
- Medical College of Wisconsin United States
- Gulf Coast Regional Blood Center United States
- Blood Systems Research Institute United States
- Bloodcenter of Wisconsin United States
Male, Mice, Knockout, Nitric Oxide Synthase Type III, rap1 GTP-Binding Proteins, Blood Pressure, Nitric Oxide, Mechanotransduction, Cellular, Models, Biological, Capillary Permeability, Vasodilation, Mice, Organ Specificity, Hypertension, Animals, Humans, Hypertrophy, Left Ventricular, Endothelium, Signal Transduction
Male, Mice, Knockout, Nitric Oxide Synthase Type III, rap1 GTP-Binding Proteins, Blood Pressure, Nitric Oxide, Mechanotransduction, Cellular, Models, Biological, Capillary Permeability, Vasodilation, Mice, Organ Specificity, Hypertension, Animals, Humans, Hypertrophy, Left Ventricular, Endothelium, Signal Transduction
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