METABOLISM OF HDL APOLIPOPROTEINS IN NORMAL & HYPOALPHALIPOPROTEINEMIC SUBJECTS

HDL水平并不总是预测早发CHD的风险。HDL是 HDL的高度异质性和某些亚组分可能更特异 CHD风险的标志物。ApoA-I和ApoA-II是两种主要的载脂蛋白 与HDL相关; apoA-II的催化作用比 apoA-I在正常人中。HDL颗粒的两个主要类别包括 LpA-I和LpA-I：A-II。已发现LpA-I，而不是LpA-I、A-II， 与早发冠心病的风险密切相关我们建立 apoA-I在LpA-I上的催化作用明显快于 apoA-I对LpA-I：A-II的影响，表明这些代谢调节 两种HDL颗粒是完全不同的。最重要的代谢 血浆LpA-I水平的决定因素是apoA-I催化速率。的 LpA-I的主要三个亚群已经基于 其大小和特征。这三个亚群具有不同的 脂质和载脂蛋白组成以及不同水平的CETP和LCAT 活性，指示不同的代谢作用。正在进行的研究 调查这些亚群的感染情况， 更好地了解大小和脂质成分如何影响LpA-I 猫 胆固醇酰基转移酶（LCAT）是一种血浆酶， 催化血浆中HDL胆固醇酯的形成。我们有 研究了HDL载脂蛋白和颗粒的代谢， 典型（完全）LCAT缺乏和部分LCAT患者 一种称为鱼眼病（FED）的缺乏症;这些疾病与 HDL水平非常低，但不增加早发冠心病的风险。 在两种类型的LCAT缺乏症中，apoA-I，尤其是apoA-II， 分解代谢明显快于对照组。LpA-I：A-II 比LpA-I分解代谢更快，导致选择性降低， LpA-I：A-II水平。这可能解释了为什么这些患者没有 尽管HDL水平较低，但过早患CHD的风险增加。正在进行 研究的重点是调查HDL代谢在其他 低HDL患者和LpA-I分解代谢率与 LpA-I：A-II有早发CHD的风险。 这些研究包括19至53岁的受试者。 45%的研究 受试者为女性。 这些研究包括两个亚洲和一个东印度 话题吧

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.