AIBP, Angiogenesis, Hematopoiesis, and Atherogenesis.

AIBP dictates both developmental processes such as angiogenesis and hematopoiesis, and pathological events such as inflammation, tumorigenesis, and atherosclerosis. Although cholesterol efflux dictates AIBP-mediated lipid raft disruption in many of the cell types, recent studies document cholesterol efflux-independent mechanism involving Cdc42-mediated cytoskeleton remodeling in macrophages. AIBP disrupts lipid rafts and impairs raft-associated VEGFR2 but facilitates non-raft-associated NOTCH1 signaling. Furthermore, AIBP can induce cholesterol biosynthesis gene SREBP2 activation, which in turn transactivates NOTCH1 and supports specification of hematopoietic stem and progenitor cells (HSPCs). In addition, AIBP also binds TLR4 and represses TLR4-mediated inflammation. In this review, we summarize the latest research on AIBP, focusing on its role in cholesterol metabolism and the attendant effects on lipid raft-regulated VEGFR2 and non-raft-associated NOTCH1 activation in angiogenesis, SREBP2-upregulated NOTCH1 signaling in hematopoiesis, and TLR4 signaling in inflammation and atherogenesis. We will discuss its potential therapeutic applications in angiogenesis and inflammation due to selective targeting of activated cells.