Apolipoprotein A-I binding protein (AIBP) has been shown to augment cholesterol efflux from endothelial cells and macrophages. In zebrafish and mice, AIBP-mediated regulation of cholesterol levels in the plasma membrane of endothelial cells controls angiogenesis. The goal of this work was to evaluate metabolic changes and atherosclerosis in AIBP loss-of-function and gain-of-function animal studies. Here, we show that mice fed a high-cholesterol, high-fat diet had exacerbated weight gain, liver steatosis, glucose intolerance, hypercholesterolemia, hypertriglyceridemia, and larger atherosclerotic lesions compared with mice. Feeding mice a high-cholesterol, normal-fat diet did not result in significant differences in lipid levels or size of atherosclerotic lesions from mice. Conversely, adeno-associated virus-mediated overexpression of AIBP reduced hyperlipidemia and atherosclerosis in high-cholesterol, high-fat diet-fed mice. Injections of recombinant AIBP reduced aortic inflammation in mice fed a short high-cholesterol, high-fat diet. Conditional overexpression of AIBP in zebrafish also reduced diet-induced vascular lipid accumulation. In experiments with isolated macrophages, AIBP facilitated cholesterol efflux to HDL, reduced lipid rafts content, and inhibited inflammatory responses to lipopolysaccharide.jlr Our data demonstrate that AIBP confers protection against diet-induced metabolic abnormalities and atherosclerosis.

Cardiovascular disease, which is often driven by hypercholesterolemia and subsequent coronary atherosclerosis, is the numberone cause of morbidity and mortality in the United States. Based on long-term epidemiological studies, high-density lipoprotein cholesterol (HDL-C) levels are inversely correlated with risk for coronary artery disease (CAD). HDL-mediated reverse cholesterol transport (RCT) is responsible for cholesterol removal from the peripheral tissues and return to the liver for final elimination. In atherosclerosis, intraplaque angiogenesis promotes plaque growth and increases plaque vulnerability. Conceivably, the acceleration of RCT and disruption of intraplaque angiogenesis would inhibit atherosclerosis and reduce CAD. We have identified a protein called apoA-I binding protein (AIBP) that augments HDL functionality by accelerating cholesterol efflux. Furthermore, AIBP inhibits vascular endothelial growth factor receptor 2 activation in endothelial cells and limits angiogenesis. 2 The following discusses the prospect of using AIBP as a novel therapeutic approach for the treatment of CAD.L. Zhu, B.S.L. Fang, Ph.D.