METABOLISM OF LIPOPROTEIN A IN HUMANS

人体脂蛋白 A 的代谢

• 批准号: 3779544
• 负责人: D J RADER
• 金额: --
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3779544
• 关键词: apolipoproteins; atherosclerosis; blood lipoprotein metabolism; coronary disorder; disease /disorder proneness /risk; genetic polymorphism; high density lipoproteins; human subject; lecithin cholesterol acyltransferase deficiency; plasminogen; protein isoforms; protein sequence; protein structure function; young adult human (21-34)

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.

HDL是高度异质性的，HDL的某些亚组分可能更多。 CHD风险的特定标志物。 载脂蛋白A-I和载脂蛋白A-II是两种主要的 与HDL相关的载脂蛋白。 HDL的两大类 颗粒包括仅含有apoA-I（LpA-I）的颗粒和含有apoA-I（LpA-I）的颗粒。 含有apoA-I和apoA-II（LpA-I：A-II）。LpA-I，但不是LpA-I：A- II，已被发现与早产儿的风险特别相关 冠心病，因此，重要的是要确定的因素， 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催化率。 为了进一步研究LpA-I 代谢，我们开发了一种方法来分离这三个 LpA-I的主要亚群基于颗粒大小。 这三 子类（大，中，小）具有不同的脂质和 载脂蛋白组成和不同水平的CETP和LCAT 活性，指示不同的代谢作用。 妇女 大LpA-I的水平显著高于男性，但不是 中等或小颗粒。 我们研究了 这些LpA-I亚类，并确定小LpA-I颗粒是 比大颗粒和中颗粒更快地分解代谢。 这是 第一次直接证明HDL颗粒的大小影响 它的分解率 正在进行的研究旨在调查 粒度影响LpA-I催化剂的机制。 这些研究包括19至47岁的受试者。 52%的研究 受试者为女性，7名为东亚人，3名为东印度人。