METABOLISM OF HDL APOLIPOPROTEINS IN NORMAL & HYPOALPHALIPOPROTEINEMIC SUBJECTS

高密度脂蛋白水平并不总是预测早产冠心病的风险。高密度脂蛋白是 高密度脂蛋白的高度异质性和某些亚组分可能更具特异性 冠心病风险的标志物。载脂蛋白A-I和载脂蛋白A-II是两种主要的载脂蛋白 与高密度脂蛋白有关；apoA-II的分解代谢慢于 正常人的载脂蛋白A-I。高密度脂蛋白颗粒的两大类包括 LPA-I和LPA-I：A-II。LPA-I，而不是LPA-I，A-II已被发现是 特别是与早产冠心病的风险有关。我们已经确立了 载脂蛋白A-I在LPA-I上的分解代谢明显快于此 载脂蛋白A-I在LPA-I：A-II上的表达，表明这些蛋白的代谢调节 两个高密度脂蛋白粒子从根本上是不同的。最重要的新陈代谢 血浆LPA-I水平的决定因素是apoA-I分解代谢率。这个 LPA-I的主要三个亚群已经被准备分离出来 关于它们的大小和特征。这三个亚群有不同的 脂质和载脂蛋白组成与CETP和LCAT的不同水平 活性，表明不同的代谢作用。正在进行的研究包括 研究这些亚群的分解代谢，以努力 更好地了解大小和脂质成分如何影响LPA-I 分解代谢。 卵磷脂：胆固醇酰基转移酶(LCAT)是一种血浆酶，它 催化血浆中高密度脂蛋白胆固醇酯的形成。我们有 研究了高密度脂蛋白和载脂蛋白的代谢。 典型(完全)LCAT缺乏症和部分LCAT缺乏症患者 缺乏症称为鱼眼病(FED)；这些疾病与 高密度脂蛋白水平非常低，但不会增加早产冠心病的风险。 在两种类型的LCAT缺乏症中，apoA-I尤其是apoA-II 分解速度比对照组快得多。此外，LPA-I：A-II 比LPA-I分解更快，导致选择性地减少 LPA-I水平：A-II。这可能解释了为什么这些患者不在 尽管他们的高密度脂蛋白水平较低，但早产冠心病的风险增加。正在进行中 研究主要集中在对其他动物高密度脂蛋白代谢的研究。 低密度脂蛋白血症患者LPA-I和LPA-I分解代谢率的相关性 LPA-I：A-II合并早发冠心病的风险。 这些研究对象的年龄在19岁到53岁之间。45%的研究 受试者为女性。这些研究包括两名亚洲人和一名东印度人 主题。

HDL levels are not always predictive of risk of premature CHD. HDL is highly heterogeneous and certain subfractions of HDL may be more specific markers of CHD risk. ApoA-I and apoA-II are the two major apolipoproteins associated with HDL; the catabolism of apoA-II is slower than that of apoA-I in normal subjects. The two major classes of HDL particles include LpA-I and LpA-I:A-II. LpA-I, but not LpA-I,A-II, has been found to be specifically associated with risk of premature CHD. We have established that the catabolism of apoA-I on LpA-I is significantly faster than that of apoA-I on LpA-I:A-II, indicating that the metabolic regulation of these two HDL particles is fundamentally divergent. The most important metabolic determinant of plasma LpA-I levels is the rate of apoA-I catabolism. The major three subpopulations of LpA-I have been preparatively isolated based on their size and characterized. These three subpopulations have different lipid and apolipoprotein composition and different levels of CETP and LCAT activity, indicative of different metabolic roles. Ongoing studies are investigating the catabolism of these subpopulations, in an effort to better understand how size and lipid composition may affect LpA-I catabolism. Lecithin:cholesterol acyltransferase (LCAT) is a plasma enzyme which catalyzes the formation of HDL cholesteryl ester in plasma. We have investigated the metabolism of HDL apolipoproteins and particles in patients with classic (complete) LCAT deficiency and with a partial LCAT deficiency termed fish-eye disease (FED); these disorders are associated with very low levels of HDL but not with increased risk of premature CHD. In both types of LCAT deficiency, apoA-I and especially apoA-II were catabolized substantially faster than in controls. Furthermore, LpA-I:A-II was catabolized faster than LpA-I, resulting in a selective decrease in levels of LpA-I:A-II. This may explain why these patients are not at increased risk for premature CHD despite their low levels of HDL. Ongoing studies are focused on the investigation of HDL metabolism in other patients with low HDL and correlation of the catabolic rates of LpA-I and LpA-I:A-II with risk of premature CHD. These studies included subjects of age 19 to 53 years. 45% of the study subjects were women. The studies included two Asian and one East Indian subject.