METABOLISM OF LPA-I AND LPA-I--A-II IN HUMANS

LPA-I 和 LPA-I--A-II 在人体中的代谢

• 批准号: 3757637
• 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/3757637
• 关键词: apolipoproteins; blood lipid; blood lipoprotein metabolism; chemical kinetics; high density lipoproteins; human subject; triglycerides

HDL are heterogeneous and the major lipoprotein particles include LpA- I,and LpA-I:A-II. Current data based on epidemiological, cell culture, as well as transgenic animal studies are consistent with LpA-I being the antiatherogenic particle within HDL. In our previous studies we have established that LpA-I is catabolized at a faster rate than LpA-I:A-II. LpA-I:A-II is fromed by the addition of apoA-II to LpA-I particles. Three subclasses of LpA-I are present in human plasma. These three subclasses designated Large, Medium, and Small have different lipid and apolipoprotein composition as well as concentrations of CETP and LCAT activities indicating the important heterogeneity of the LpA-I particles. Women have a higher plasma concentration than men of only the Large LpA-I particle with similar concentration of the Middle and Small LpA-I particles. The metabolism of the three LpA-I particles was investigated in normal control subjects. The catabolism of the Small LpA-I was the fastest of the three LpA-I particles clearly establishing that the catabolism of LpA-I is critically dependent on the size of the LpA-I particle. To gain insight into the metabolism of LpA-I and LpA-I:A-II kinetic studies were performed in fifty normolipidemic subjects and the associations with lipids and apolipoprotein levels determined. Triglyceride levels inversely correlated with only LpA-I. ApoA-I levels were most strongly correlated with the catabolic rate. ApoA-II levels were only correlated with synthesis rate. Plasma LpA-I levels are correlated with the catabolism of both apoA-I and apoA-II while LpA-I:A- II levels were correlated with the synthesis rates of apoA-I and apoA-II. Based on multiple regression analysis the production rate of apoA-II is the only independent kinetic parameter determining the plasma LpA-I levels. Further studies are underway to investigate additional parameters that modulate LpA-I and LpA-I:A-II metabolism. These studies included subjects of age 19 to 47. 52% of the study subjects were women, seven were Asian, and three were Indian.

HDL是异质性的，主要的脂蛋白颗粒包括LpA- I和LpA-I：A-II。 基于流行病学，细胞培养， 以及转基因动物研究与LpA-I是 HDL中的抗动脉粥样硬化颗粒。 在我们以前的研究中， 确定LpA-I以比LpA-I：A-II更快的速率分解代谢。 LpA-I：A-II是通过将apoA-II添加到LpA-I颗粒中形成的。 人血浆中存在LpA-I的三个亚类。 这三 指定为大型、中型和小型的子类具有不同的脂质和 载脂蛋白组成以及CETP和LCAT浓度 活性表明LpA-I颗粒的重要异质性。 女性仅大LpA-I的血浆浓度高于男性 中等和小LpA-I浓度相似的颗粒 粒子 研究了三种LpA-I颗粒的代谢 在正常对照组中。 小LpA-I的目录是 最快的三个LpA-I粒子清楚地表明， LpA-I的催化活性严重依赖于LpA-I的大小， 粒子 了解LpA-I和LpA-I：A-II的代谢动力学 在50名血脂正常的受试者中进行了研究， 与血脂和载脂蛋白水平的关系。 甘油三酯水平仅与LpA-I呈负相关。ApoA-I水平 与分解代谢率相关性最强。ApoA-II水平 仅与合成速率相关。 血浆LpA-I水平是 与apoA-I和apoA-II的催化活性相关，而LpA-I：A- II水平与apoA-I和apoA-II的合成速率相关。 根据多元回归分析，apoA-II的产生率为 决定血浆LpA-I的唯一独立动力学参数 程度. 正在进行进一步的研究， 调节LpA-I和LpA-I：A-II代谢的参数。 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名亚洲人，3名印度人。