METABOLISM OF LIPOPROTEIN A IN HUMANS

高密度脂蛋白是高度异质性的，高密度脂蛋白的某些亚组分可能比 冠心病风险的特定标记物。载脂蛋白A-I和载脂蛋白A-II是 载脂蛋白与高密度脂蛋白相关。高密度脂蛋白的两大类 粒子包括只含有apoA-I(LPA-I)的粒子和那些 含有apoA-I和apoA-II(LPA-I：A-II)。LPA-I，而非LPA-I：A- II，已被发现与早产的风险特别相关 因此，重要的是要确定哪些因素 影响血浆LPA-I水平。我们之前已经建立了 血浆LPA-I水平最重要的代谢决定因素是 LPA-I分解代谢率。为了进一步研究LPA-I 新陈代谢，我们开发了一种准备分离这三种细菌的方法 基于颗粒大小的LPA-I的主要亚群。这三个人 亚类(大、中、小)具有不同的脂类和 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。女人有 显著高于大LPA-I的男性，但不是 中、小颗粒。我们研究了阿司匹林的体内代谢 这些LPA-I亚类并确定小的LPA-I粒子是 比大颗粒和中等颗粒分解更快。这是 高密度脂蛋白颗粒大小影响的第一个直接证明 它的分解代谢率。正在进行的研究旨在调查 颗粒大小影响LPA-I分解代谢的机制。 这些研究对象的年龄在19岁到47岁之间。52%的研究 受试者为女性，7名东亚人，3名东印度人。

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 two major classes of HDL particles include those containing only apoA-I (LpA-I) and those containing both apoA-I and apoA-II (LpA-I:A-II). LpA-I, but not LpA-I:A- II, has been found to be specifically associated with risk of premature CHD, and therefore it is important to determine the factors that influence the plasma levels of LpA-I. We have previously established that the most important metabolic determinant of plasma LpA-I levels is the rate of LpA-I catabolism. In order to further investigate LpA-I metabolism, we developed a method to preparatively isolate the three major subpopulations of LpA-I based on particle size. These three subclasses (Large, Medium, and Small) have different lipid and apolipoprotein composition and different levels of CETP and LCAT activity, indicative of different metabolic roles. Women have significantly higher levels than men of the Large LpA-I, but not of the Medium or Small particles. We investigated the in vivo metabolism of these LpA-I subclasses and determined that the Small LpA-I particles are more rapidly catabolized than the Large and Medium particles. This is the first direct demonstration that the size of an HDL particle affects its catabolic rate. Ongoing studies are directed toward investigating the mechanism by which particle size affects LpA-I catabolism. These studies included subjects of age 19 to 47 years. 52% of the study subjects were women, seven were East Asian, and three were East Indian.