Abstract 8: The Membrane-associated Guanylate Kinase Ww and Pdz Domain-containing Protein 1 magi1 is Required for Disturbed Flow-induced Endothelial Inflammation and Atherosclerotic Plaque Formation

Rationale: Major chronic inflammatory diseases including inflammatory bowel disease and psoriasis are clinically associated with accelerated atherosclerosis and increased risk of cardiovascular diseases (CVD). Atherosclerosis has long been recognized as an inflammatory process, which is initiated by the inflammation and dysfunction of endothelial cells (ECs). Genome-wide association study (GWAS) has identified a significant association between the deletion in ADAMTS9-MAGI1 locus with inflammatory bowel disease and psoriasis, suggesting a potential involvement of MAGI1 in EC inflammation and its associated events. Objective: To investigate the role and regulatory mechanism of MAGI1 as well as MAGI1 post-translational modification in EC inflammation, after various pro-atherogenic stimuli. Methods and Results: MAGI1 depletion significantly inhibits NF-κB activation and adhesion molecule expression induced by various pro-atherogenic stimuli in both in vitro and in vivo. We show that p90RSK associates with MAG...