AIP1-mediated stress signaling in atherosclerosis and arteriosclerosis.
AIP1 (ASK1-interacting protein-1; encoded by the DAB2IP gene), a signaling scaffolding protein, is abundantly expressed in vascular endothelial cells (EC). While it was initially discovered as an apoptosis signal-regulating kinase 1 (ASK1)-interacting protein, AIP1 broadly suppresses inflammatory responses triggered by cytokines and stresses such as TNF, LPS, VEGF, and endoplasmic reticulum (ER) stress in EC (therefore, AIP1 is an anti-inflammatory protein). Human genome-wide association study (GWAS) has identified DAB2IP gene variants conferring susceptibility to cardiovascular diseases. Consistently, a global or vascular EC-specific deletion of DAB2IP in mice strongly enhances inflammatory responses and exacerbates atherosclerosis and graft arteriosclerosis progression in mouse models. Mechanisms for AIP1 function and regulation associated with human cardiovascular diseases need further investigations.
Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China.
Jiqin
J
Zhang
Huanjiao Jenny
HJ
Zhou
Weidong
W
Ji
Wang
W
Min
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001161:Arteriosclerosis / Q000235:genetics* / Q000378:metabolism; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics*; D055106:Genome-Wide Association Study; D051528:Guanylate Kinases; D006801:Humans; D018384:Oxidative Stress / Q000235:genetics*; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D051528:Guanylate Kinases; C485777:MAGI2 protein, human