Yamashita S, Hirano K, Sakai N, Matsuzawa Y
Department of Internal Medicine and Molecular Science, Graduate School of Medicine, B5, Osaka University, 2-2 Yamadaoka, Suita, 565-0871, Osaka, Japan.
Biochim Biophys Acta. 2000 Dec 15;1529(1-3):257-75. doi: 10.1016/s1388-1981(00)00164-5.
Plasma cholesteryl ester transfer protein (CETP) facilitates the transfer of cholesteryl ester (CE) from high density lipoprotein (HDL) to apolipoprotein B-containing lipoproteins. Since CETP regulates the plasma levels of HDL cholesterol and the size of HDL particles, CETP is considered to be a key protein in reverse cholesterol transport, a protective system against atherosclerosis. CETP, as well as plasma phospholipid transfer protein, belongs to members of the lipid transfer/lipopolysaccharide-binding protein (LBP) gene family, which also includes the lipopolysaccharide-binding protein (LBP) and bactericidal/permeability-increasing protein. Although these four proteins possess different physiological functions, they share marked biochemical and structural similarities. The importance of plasma CETP in lipoprotein metabolism was demonstrated by the discovery of CETP-deficient subjects with a marked hyperalphalipoproteinemia (HALP). Two common mutations in the CETP gene, intron 14 splicing defect and exon 15 missense mutation (D442G), have been identified in Japanese HALP patients with CETP deficiency. The deficiency of CETP causes various abnormalities in the concentration, composition, and functions of both HDL and low density lipoprotein. Although the pathophysiological significance of CETP in terms of atherosclerosis has been controversial, the in vitro experiments showed that large CE-rich HDL particles in CETP deficiency are defective in cholesterol efflux. Epidemiological studies in Japanese-Americans and in the Omagari area where HALP subjects with the intron 14 splicing defect of CETP gene are markedly frequent, have shown an increased incidence of coronary atherosclerosis in CETP-deficient patients. The current review will focus on the recent findings on the molecular biology and pathophysiological aspects of plasma CETP, a key protein in reverse cholesterol transport.
血浆胆固醇酯转运蛋白（CETP）促进胆固醇酯（CE）从高密度脂蛋白（HDL）转移至含载脂蛋白B的脂蛋白。由于CETP调节HDL胆固醇的血浆水平以及HDL颗粒大小，因此CETP被认为是逆向胆固醇转运中的关键蛋白，逆向胆固醇转运是一种抗动脉粥样硬化的保护系统。CETP以及血浆磷脂转运蛋白属于脂质转运/脂多糖结合蛋白（LBP）基因家族成员，该家族还包括脂多糖结合蛋白（LBP）和杀菌/通透性增加蛋白。尽管这四种蛋白具有不同的生理功能，但它们在生化和结构上有显著的相似性。血浆CETP在脂蛋白代谢中的重要性通过发现CETP缺陷的显著高α脂蛋白血症（HALP）患者得以证明。在日本患有CETP缺陷的HALP患者中已鉴定出CETP基因的两个常见突变，即内含子14剪接缺陷和外显子15错义突变（D442G）。CETP缺乏会导致HDL和低密度脂蛋白在浓度、组成和功能方面出现各种异常。尽管CETP在动脉粥样硬化方面的病理生理意义一直存在争议，但体外实验表明，CETP缺乏时富含CE的大HDL颗粒在胆固醇流出方面存在缺陷。对日裔美国人以及小牧地区（该地区具有CETP基因内含子14剪接缺陷的HALP患者明显较多）的流行病学研究表明，CETP缺陷患者冠状动脉粥样硬化的发病率增加。本综述将聚焦于血浆CETP（逆向胆固醇转运中的关键蛋白）在分子生物学和病理生理学方面的最新研究结果。
