Selective role of Nck1 in atherogenic inflammation and plaque formation.

ABSTRACT: Although the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) established the role of treating inflammation in atherosclerosis, our understanding of endothelial activation at atherosclerosis-prone sites remains limited. Disturbed flow at atheroprone regions primes plaque inflammation by enhancing endothelial NF-κB signaling. Herein, we demonstrate a role for the Nck adaptor proteins in disturbed flow-induced endothelial activation. Although highly similar, only Nck1 deletion, but not Nck2 deletion, limited flow-induced NF-κB activation and proinflammatory gene expression. Nck1-knockout mice showed reduced endothelial activation and inflammation in both models, disturbed flow- and high fat diet-induced atherosclerosis, whereas Nck2 deletion did not. Bone marrow chimeras conf

SUBMITTER: Alfaidi M 

PROVIDER: S-EPMC8011212 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature