HDL METABOLISM IN HYPOALPHALIPOPROTEINEMIA

血浆高密度脂蛋白胆固醇和载脂蛋白A-I与高密度脂蛋白胆固醇水平呈负相关。 早发心血管疾病（CVD）。 目前的筛选 测试HDL水平的程序将识别出HDL水平低的个体， 需要评估CVD风险增加。 并不是所有的低 HDL增加了CVD的风险。 遗传性疾病的特点是低 与CVD风险显著增加无关的HDL水平包括 LCAT缺乏症、鱼眼病和丹吉尔病。 最近我们 家族性低脂蛋白血症（F Hypoalpha） HDL为7 - 15 mg/dl，无早发性CVD。 我们已经进行了放射性标记的LpA-I和LpA-I：A-II动力学研究， LCAT缺乏症和家族性低脂蛋白血症患者 没有心脏病。 LpA-I和LpA-I：A-II，两种主要的脂蛋白 HDL中的颗粒，不同的是它们对CVD的保护。 几行 的证据表明，LpA-I而不是LpA-I：A-II是主要的 抗动脉粥样硬化脂蛋白颗粒。在LCAT的动力学研究中， 缺乏型患者apoA-I对LpA-I：A-II的催化作用， 显著快于apoA-I对LpA-I的作用，导致选择性 LpA-I：A-II的血浆水平成比例降低。 因此存在 对降低血浆LpA-I水平的作用相对较小。 这可能是一个潜在的机制，因为病人 低HDL的LCAT缺乏症患者， 心血管疾病 5例F低α先证者的动力学研究 无CVD显示LpA-I和LpA-I：A-II均迅速 分解代谢导致低HDL水平。LpA-I：A-II的催化剂是 比LpA-I稍快，导致正常或增加的 血浆LpA-I/LpA-I：A-II。 这些研究的综合结果清楚地表明， 低脂蛋白血症是异质性的，并不是所有的患者 低HDL会增加早发CVD的风险。 代谢研究表明， 表明LpA-I和LpA-I：A-II的代谢受到影响 LCAT缺乏症和F低α患者。这些数据将 提供了新的方法来确定哪些个人与 高密度脂蛋白低的人患早发性心血管疾病的风险增加。

Plasma HDL cholesterol and apoA-I are inversely correlated with the development of premature cardiovascular disease (CVD). Current screening programs testing HDL levels will identify individuals with low HDL that require evaluation for increased CVD risk. Not all individuals with low HDL are at increased CVD risk. Genetic diseases characterized by low levels of HDL not associated with markedly increased CVD risk include LCAT deficiency, Fish Eye Disease, and Tangier disease. Recently we identified kindreds with familial hypoalphalipoproteinemia (F Hypoalpha) with HDL from 7 to 15 mg/dl and no premature CVD. We have performed radiolabeled LpA-I, and LpA-I:A-II kinetic studies in patients with LCAT deficiency, and familial hypoalphalipoproteinemia without heart disease. LpA-I and LpA-I:A-II, the two major lipoprotein particles in HDL, differ in their protection against CVD. Several lines of evidence indicate that LpA-I not LpA-I:A-II is the major antiatherogenic lipoprotein particle in HDL. In kinetic studies of LCAT deficient patients the catabolism of apoA-I on LpA-I:A-II is significantly faster that of apoA-I on LpA-I resulting in a selective proportional decrease in the plasma levels of LpA-I:A-II. Thus there is a relatively sparing effect on the reduction of plasma LpA-I levels. This may be one of the potential mechanisms for the reason that patients with LCAT deficiency with low HDL are not at increased risk for premature cardiovascular disease. Kinetic studies in five F Hypoalpha probands without CVD revealed that both LpA-I and LpA-I:A-II are rapidly catabolized leading to low HDL levels. Catabolism of LpA-I:A-II is slightly faster than LpA-I leading to a normal or increased ratio of plasma LpA-I/LpA-I:A-II. The combined results from these studies have clearly shown that hypoalphalipoproteinemia is heterogeneous and that not all patients with low HDL have an increased risk of premature CVD. Metabolic studies have shown that the metabolism of LpA-I and LpA-I:A-II are effected independently LCAT deficiency and F Hypoalpha patients. These data will provide new approaches to the identification of which individuals with low HDL are at increased risk of premature CVD.