Department of Cardiovascular Sciences, Center for Cardiovascular Regeneration, Houston Methodist DeBakey Heart and Vascular Center, Houston Methodist, Houston, Texas.
Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, New York.
Curr Opin Lipidol. 2019 Jun;30(3):218-223. doi: 10.1097/MOL.0000000000000596.
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.
最近的研究表明，分泌型载脂蛋白 A-I 结合蛋白（AIBP）在胆固醇外排和脂筏调节中具有重要作用。本文讨论了这些发现与血管生成和炎症的关系。
脂筏是富含胆固醇和神经鞘磷脂的膜结构域，其中许多受体复合物在激活时组装。AIBP 通过与激活的巨噬细胞和小胶质细胞中的 toll 样受体-4（TLR4）结合，介导选择性胆固醇外排，从而逆转激活细胞中的脂筏增加。最近的文章报道了 AIBP 对血管内皮生长因子受体-2、Notch1 和 TLR4 功能的调节。在斑马鱼和小鼠动物模型中，AIBP 缺乏导致血管生成加速、炎症增加和动脉粥样硬化加剧。在化疗诱导的多发性神经病的小鼠模型中，鞘内给予重组 AIBP 可减少脊神经轴突炎症并逆转持续性疼痛状态。吸入重组 AIBP 可减轻小鼠脂多糖诱导的急性肺损伤。这些发现从 AIBP 的另一种功能，即 NAD(P)H 水合酶差向异构体酶，演变为胆固醇转运和脂筏调节因子的角度进行了讨论。
AIBP 调节脂质筏和相关细胞过程的新发现可能为血管生成和炎症性疾病提供新的治疗途径。
