METABOLISM OF HDL APOLIPOPROTEINS IN NORMAL & HYPOALPHALIPOPROTEINEMIC SUBJECTS

血浆HDL胆固醇和apoA-I在流行病学上与 早发冠心病的风险，但并不总是预测 在个别患者中。 一个例子是LCAT的遗传综合征 缺陷LCAT是一种催化HDL形成的血浆酶 血浆胆固醇酯。经典（完全）LCAT患者 缺乏和部分LCAT缺乏称为鱼眼病 (FED)HDL和apoA-I水平很低，但没有增加 过早CHD的风险。我们研究了HDL apoA-I和apoA-II， 五名患有不同类型LCAT缺乏症的患者同时使用这两种方法 稳定同位素内源标记和外源标记 放射性示踪剂 我们发现apoA-I尤其是apoA-II 分解代谢大大快于对照组，占 血浆中的低水平。 HDL颗粒的两个主要类别包括仅含有 apoA-I（LpA-I）和含有apoA-I和apoA-II的那些（LpA-I：A-II）。 LpA-I，而不是LpA-I：A-II，已被发现与 有早发冠心病的风险我们之前已经确定，在正常情况下， 受试者apoA-I对LpA-I的催化作用明显快于 apoA-I对LpA-I：A-II的代谢调节 这两种HDL颗粒的性质是完全不同的。 在LCAT 而LpA-I：A-II缺乏的患者， 比LpA-I更快，导致LpA-I：A-II的血浆水平， 比LpA-I低得多。这可能是一个 观察结果解释这些患者的 尽管HDL水平较低，但仍有过早患CHD的风险。我们还 研究了其他五名患者的HDL代谢， 高密度脂蛋白水平很低但没有冠心病在这些患者中，我们还发现 apoA-I、apoA-II和LpA-I：A-II的快速催化作用， 这些载脂蛋白的低血浆水平。这些研究证明 并不是所有低HDL综合征都必然导致早产儿 LpA-I：A-II迅速升高可能是HDL降低的原因之一 与CHD风险增加无关。

Plasma HDL cholesterol and apoA-I are epidemiologically associated with risk of premature coronary heart disease, but are not always predictive in individual patients. One example are the genetic syndromes of LCAT deficiency. LCAT is a plasma enzyme which catalyzes the formation of HDL cholesteryl ester in plasma. Patients with classic (complete) LCAT deficiency and with a partial LCAT deficiency termed fish-eye disease (FED) have very low levels of HDL and apoA-I but do not have an increased risk of premature CHD. We investigated HDL apoA-I and apoA-II in a total of five patients with different types of LCAT deficiency using both endogenous labeling with stable isotopes and exogenously labeled radiotracers. We found that apoA-I and especially apoA-II were catabolized substantially faster than in control subjects, accounting for their low levels in plasma. 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. We have previously established that in normal subjects 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. In the LCAT deficient patients, however, the catabolism of LpA-I:A-II was markedly faster than that of LpA-I, resulting in plasma levels of LpA-I:A-II that were proportionately much lower than those of LpA-I. This could be an explanation for the observation that these patients are not at increased risk for premature CHD despite their low levels of HDL. We have also investigated HDL metabolism in a series of five other patients who also have very low levels of HDL but no CHD. In these patients we also found rapid catabolism of apoA-I, apoA-II, and LpA-I:A-II accounting for the low plasma levels of these apolipoproteins. These studies demonstrate that not all syndromes of low HDL necessarily predispose to premature CHD, and that rapid catabolism of LpA-I:A-II may be one cause of low HDL not associated with increased risk of CHD.