Recent studies demonstrate an important role of the secreted apolipoprotein A-I binding protein (AIBP) in regulation of cholesterol efflux and lipid rafts. The article discusses these findings in the context of angiogenesis and inflammation.
Lipid rafts are cholesterol-rich and sphingomyelin-rich membrane domains in which many receptor complexes assemble upon activation. AIBP mediates selective cholesterol efflux, in part via binding to toll-like receptor-4 (TLR4) in activated macrophages and microglia, and thus reverses lipid raft increases in activated cells. Recent articles report AIBP regulation of vascular endothelial growth factor receptor-2, Notch1 and TLR4 function. In zebrafish and mouse animal models, AIBP deficiency results in accelerated angiogenesis, increased inflammation and exacerbated atherosclerosis. Spinal delivery of recombinant AIBP reduces neuraxial inflammation and reverses persistent pain state in a mouse model of chemotherapy-induced polyneuropathy. Inhalation of recombinant AIBP reduces lipopolysaccharide-induced acute lung injury in mice. These findings are discussed in the perspective of AIBP's proposed other function, as an NAD(P)H hydrate epimerase, evolving into a regulator of cholesterol trafficking and lipid rafts.
Novel findings of AIBP regulatory circuitry affecting lipid rafts and related cellular processes may provide new therapeutic avenues for angiogenic and inflammatory diseases.
aDepartment of Cardiovascular Sciences, Center for Cardiovascular Regeneration, Houston Methodist DeBakey Heart and Vascular Center, Houston Methodist, Houston, Texas
bDepartment of Cell and Developmental Biology, Weill Cornell Medical College, New York, New York
cDepartment of Medicine, University of California, San Diego, La Jolla, California, USA
Correspondence to Longhou Fang, PhD, Department of Cardiovascular Sciences, Houston Methodist Research Institute, 6670 Bertner Ave., Mail Stop: R10-South, Houston, TX 77030, USA. Tel: +1 713 363 9012; e-mail: email@example.com