Hugh Sinclair Lecture: The regulation and remodelling of HDL by plasma factors
Hugh Sinclair Lecture: The regulation and remodelling of HDL by plasma factors
复制标题
DOI：
10.1016/s1567-5688(02)00041-7
复制
发表时间：
2002-12-01
影响因子：
--
通讯作者：
Barter, PJ
中科院分区：
文献类型：
--
作者：
Barter, PJ
高密度脂蛋白(HDL)起源于无脂或贫脂的载脂蛋白，主要在细胞外获得脂肪。它们在三磷酸腺苷结合盒A L转运体的推动下接受细胞中的磷脂，形成β迁移前盘状高密度脂蛋白，是从细胞膜释放的胆固醇的有效受体。盘状高密度脂蛋白中的胆固醇被卵磷脂：胆固醇酰基转移酶(LCAT)酯化，在这个过程中，前β迁移盘转化为α迁移的球形高密度脂蛋白。球形高密度脂蛋白进一步被胆固醇酯转移蛋白(CETP)和肝脂酶重塑，CETP将胆固醇酯从高密度脂蛋白转移到其他脂蛋白，肝脏脂肪酶在减小高密度脂蛋白尺寸并导致前β迁移的、缺乏脂肪的载脂蛋白(Apo)A-I从颗粒中解离的过程中水解高密度脂蛋白甘油三酯。迁移前、缺乏脂质的载脂蛋白A-I也是磷脂转移蛋白重塑高密度脂蛋白的产物。因此，载脂蛋白A-I作为高密度脂蛋白高度动态新陈代谢的一部分，在贫脂和脂类相关形式之间循环。另一种主要的高密度脂蛋白apoA-II在LCAT介导的颗粒融合过程中被掺入含有apoA-I的颗粒中。高密度脂蛋白的胞外组装和重塑不仅在高密度脂蛋白的调节中起着重要作用，而且为治疗干预提供了潜在的靶点。这方面的一个例子是CETP抑制剂的开发。(C)2002爱思唯尔科学爱尔兰有限公司。保留所有权利。
High density lipoproteins (HDLs) originate as lipid-free or lipid-poor apolipoproteins that acquire most of their lipid in the extracellular space. They accept phospholipids from cells in a process promoted by the ATP binding cassette A l transporter to form prebeta-migrating discoidal HDL that are efficient acceptors of cholesterol released from cell membranes. The cholesterol in discoidal HDL is esterified by lecithin: cholesterol acyltransferase (LCAT) in a process that converts the prebeta-migrating disc into an alpha-migrating, spherical HDL. Spherical HDL are further remodelled by cholesteryl ester transfer protein (CETP) that transfers cholesteryl esters from HDL to other lipoproteins and by hepatic lipase that hydrolyses HDL triglyceride in processes that reduce HDL size and lead to the dissociation of prebeta-migrating, lipid-poor apolipoprotein (apo)A-I from the particle. Prebetamigrating, lipid-poor apoA-I is also generated as a product of the remodelling of HDL by phospholipid transfer protein. Thus, apoA-I cycles between lipid-poor and lipid associated forms as part of a highly dynamic metabolism of HDL. The other main HDL apolipoprotein, apoA-II is incorporated into apoA-I-containing particles in a process of particle fusion mediated by LCAT. Extracellular assembly and remodelling of HDL not only plays a major role in HDL regulation but also provides potential targets for therapeutic intervention. One example of this is the development of inhibitors of CETP. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.