Nck1, But Not Nck2, Mediates Disturbed Flow-Induced p21-Activated Kinase Activation and Endothelial Permeability.

ABSTRACT: Background Alteration in hemodynamic shear stress at atheroprone sites promotes endothelial paracellular pore formation and permeability. The molecular mechanism remains unknown. Methods and Results We show that Nck (noncatalytic region of tyrosine kinase) deletion significantly ameliorates disturbed flow-induced permeability, and selective isoform depletion suggests distinct signaling mechanisms. Only Nck1 deletion significantly reduces disturbed flow-induced paracellular pore formation and permeability, whereas Nck2 depletion has no significant effects. Additionally, Nck1 re-expression, but not Nck2, restores disturbed flow-induced permeability in Nck1/2 knockout cells, confirming the noncompensating roles. In vivo, using the partial carotid ligation model of disturbed flow, Nck1 knockou

SUBMITTER: Alfaidi M 

PROVIDER: S-EPMC7428973 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature