| First Author | Lakshmikanthan S | Year | 2015 |
| Journal | EMBO Rep | Volume | 16 |
| Issue | 5 | Pages | 628-37 |
| PubMed ID | 25807985 | Mgi Jnum | J:222867 |
| Mgi Id | MGI:5645841 | Doi | 10.15252/embr.201439846 |
| Citation | Lakshmikanthan S, et al. (2015) Rap1 promotes endothelial mechanosensing complex formation, NO release and normal endothelial function. EMBO Rep 16(5):628-37 |
| abstractText | 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. |
