丹吉尔病
ABCA1
胆固醇
内科学
载脂蛋白B
内分泌学
高密度脂蛋白
脂蛋白
生物
载脂蛋白A1
中密度脂蛋白
极低密度脂蛋白
医学
运输机
生物化学
基因
作者
Bela F. Asztalos,Ernst J. Schaefer
标识
DOI:10.1016/s0002-9149(02)03383-0
摘要
The role of low-density lipoprotein (LDL) cholesterol in coronary artery disease (CAD) and the impact of therapeutic agents on LDL cholesterol are well established. Less is known about the role of high-density lipoprotein (HDL) cholesterol and even less about the role of the different HDL subspecies in CAD. HDL particles vary in size and density, mainly because of differences in the number of apolipoprotein (apo) particles and the amount of cholesterol ester in the core of HDL. Apo A-I is essential and, together with lipid, sufficient for the formation of HDL particles. Apo A-I–containing HDL particles play a primary role in cholesterol efflux from membranes, at least in part through interactions with the adenosine triphosphate–binding cassette transporter A1 (ABCA1). Patients with Tangier disease have mutations in the gene encoding ABCA1, which result in functionally impaired protein, a marked deficiency in HDL cholesterol, and a high risk of premature CAD. Our studies of apo A-I–containing HDL subpopulations in various patient populations reveal that patients homozygous for Tangier disease have only the pre-β1 HDL subspecies. Tangier heterozygotes are severely depleted in the larger α- and pre-α–mobility subspecies. Patients with low HDL cholesterol levels and those with CAD also show deficiencies in the α1 and pre-α1–3 HDL subspecies. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) increase the levels of the large α1 and pre-α1 subpopulations and decrease the level of the small α3 subpopulation. Thus, atorvastatin, for example, significantly moves the distribution of HDL particles toward normal, followed by simvastatin, pravastatin, and lovastatin in decreasing order of efficiency. A new statin, rosuvastatin, produces greater increases in HDL cholesterol than atorvastatin, but its effect on HDL particle distribution is yet to be determined.
科研通智能强力驱动
Strongly Powered by AbleSci AI