Accéder au contenu
Merck

NOTCH1 is a mechanosensor in adult arteries.

Nature communications (2017-11-22)
Julia J Mack, Thiago S Mosqueiro, Brian J Archer, William M Jones, Hannah Sunshine, Guido C Faas, Anais Briot, Raquel L Aragón, Trent Su, Milagros C Romay, Austin I McDonald, Cheng-Hsiang Kuo, Carlos O Lizama, Timothy F Lane, Ann C Zovein, Yun Fang, Elizabeth J Tarling, Thomas Q de Aguiar Vallim, Mohamad Navab, Alan M Fogelman, Louis S Bouchard, M Luisa Iruela-Arispe
RÉSUMÉ

Endothelial cells transduce mechanical forces from blood flow into intracellular signals required for vascular homeostasis. Here we show that endothelial NOTCH1 is responsive to shear stress, and is necessary for the maintenance of junctional integrity, cell elongation, and suppression of proliferation, phenotypes induced by laminar shear stress. NOTCH1 receptor localizes downstream of flow and canonical NOTCH signaling scales with the magnitude of fluid shear stress. Reduction of NOTCH1 destabilizes cellular junctions and triggers endothelial proliferation. NOTCH1 suppression results in changes in expression of genes involved in the regulation of intracellular calcium and proliferation, and preventing the increase of calcium signaling rescues the cell-cell junctional defects. Furthermore, loss of Notch1 in adult endothelium increases hypercholesterolemia-induced atherosclerosis in the descending aorta. We propose that NOTCH1 is atheroprotective and acts as a mechanosensor in adult arteries, where it integrates responses to laminar shear stress and regulates junctional integrity through modulation of calcium signaling.

MATÉRIAUX
Référence du produit
Marque
Description du produit

Sigma-Aldrich
Dextrane from Leuconostoc spp., Mr 450,000-650,000
Sigma-Aldrich
Anticorps monoclonal de souris anti-tubuline acétylée antibody produced in mouse, clone 6-11B-1, purified from hybridoma cell culture
Sigma-Aldrich
Méthanol, anhydrous, 99.8%
Sigma-Aldrich
Anti-β-Catenin antibody produced in rabbit, whole antiserum
Sigma-Aldrich
Anticorps anti-Klf2, serum, from rabbit