Low high-density lipoprotein cholesterol as a risk factor in coronary heart disease - A working group report
Low high-density lipoprotein cholesterol as a risk factor in coronary heart disease - A working group report
复制标题
DOI：
10.1161/01.cir.103.17.2213
复制
发表时间：
2001-05-01
期刊：
影响因子：
37.8
通讯作者：
Gotto, AM
中科院分区：
文献类型：
--
作者：
Gotto, AM
LCAT缺乏可显著降低HDL-C（降至10 mg/dL [0.3 mmol/L]）和apoA-I浓度，11两者均不常与早发CHD相关。高HDL-C浓度的几种遗传原因已被报道，包括CETP和肝脂肪酶基因缺陷和脂蛋白脂肪酶多态性。CETP促进胆固醇酯在脂蛋白之间的转移，9遗传性CETP缺乏导致胆固醇酯和apoA-I的延迟性催化，导致HDL-C和apoA-I浓度显著增加。12尽管预期这些升高具有保护作用，但有证据表明，遗传性CETP缺乏导致的胆固醇转运受损可能与早发冠心病风险增加有关。RCT过程的另一个重要组成部分是磷脂转移蛋白（PLTP）。PLTP促进磷脂在脂蛋白之间的转移，并诱导HDL转化，其将均质HDL部分重塑为类似于前HDL颗粒的大小颗粒的群体，即膜胆固醇的初始受体。通过产生初始胆固醇受体，PLTP增加了RCT过程的能力。15对PLTP敲除小鼠的研究16，17表明，磷脂向HDL的转移可能在HDL成熟中起重要作用，当该过程不存在时，颗粒以增加的速率分解代谢。因此，HDL的形成可能涉及两个步骤。第一种是ABC 1催化apoA-I形成前-HDL颗粒，第二种是PLTP和LCAT催化前-HDL形成成熟HDL。肝脂酶是HDL代谢的另一个关键酶，主要位于肝窦的肝细胞中，水解TG和HDL的磷脂，导致HDL颗粒尺寸减小。这反过来又导致HDL催化剂的增加和HDL水平的降低。十二，十八
LCAT deficiencies markedly reduce HDL-C (to 10 mg/dL [0.3 mmol/L]) and apoA-I concentrations, 11 neither is commonly associated with premature CHD. Several genetic causes of high HDL-C concentrations have been reported, including defects in the genes for CETP and hepatic lipase and polymorphism of lipoprotein lipase. CETP facilitates the transfer of cholesteryl esters among lipoproteins, 9 and genetic CETP deficiency leads to delayed catabolism of both cholesteryl ester and apoA-I, resulting in marked increases in HDL-C and apoA-I concentrations. 12 Despite the expected protective effects of these elevations, evidence suggests that impaired cholesterol transport resulting from genetic CETP deficiency may be associated with an increased risk of premature CHD. 13 Another important component of the RCT process is phospholipid transfer protein (PLTP). PLTP facilitates the transfer of phospholipids between lipoproteins and induces HDL conversion, which remodels the homogeneous HDL fraction into populations of large and small particles similar to pre--HDL particles, the initial acceptors of membrane cholesterol. 14 By producing initial cholesterol acceptors, PLTP increases the capacity of the RCT process. 15 Investigations in PLTP knockout mice16, 17 have indicated that the transfer of phospholipids to HDL may play an essential role in HDL maturation and that when this process is absent, particles are catabolized at an increased rate. Therefore, it seems that 2 steps may be involved in HDL formation. The first involves catalyzation by ABC1 acting on apoA-I to form pre--HDL particles, and the second involves catalyzation by PLTP and LCAT acting on pre-HDL to produce mature HDL.Hepatic lipase, another key enzyme involved in HDL metabolism, is localized mainly to hepatocytes of the hepatic sinusoids, where it hydrolyses TG and the phospholipid of HDL, causing a reduction in HDL particle size. This in turn leads to an increase in HDL catabolism and the lowering of HDL levels. 12, 18