CHOLESTEROL NET TRANSPORT, ESTERIFICATION, AND TRANSFER IN HUMAN HYPERLIPIDEMIC PLASMA
CHOLESTEROL NET TRANSPORT, ESTERIFICATION, AND TRANSFER IN HUMAN HYPERLIPIDEMIC PLASMA
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DOI：
10.1172/jci110789
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发表时间：
1983-01-01
影响因子：
15.9
通讯作者：
TUN, P
中科院分区：
文献类型：
--
作者：
FIELDING, PE;FIELDING, CJ;TUN, P
本文测定了22例原发性高脂血症患者和10例血脂正常者的血浆胆固醇酯化、胆固醇酯在脂蛋白间的转移和胆固醇在脂蛋白与培养细胞间的转运。在高β脂蛋白血症，血浆低密度脂蛋白水平的增加与胆固醇酯转移率的降低，并与成纤维细胞和他们的血浆培养基之间的正常方向的固醇运输逆转。尽管血浆卵磷脂/胆固醇酰基转移酶活性水平在正常范围内，但细胞从血浆中净摄取甾醇，而不是从细胞净转运至培养基。在异常β脂蛋白血症，酯化率增加高于正常水平，但胆固醇酯转移减少和细胞和血浆介质之间的固醇运输方向被逆转，在高β脂蛋白血症组。在高β-脂蛋白血症中，心血管疾病受试者的代谢模式与高β-脂蛋白血症组相似。该组中没有心血管疾病症状的受试者显示出正常的固醇转运方向、脂蛋白之间胆固醇酯转移的正常或升高的速率，以及血浆中固醇酯化的升高速率，其随着血浆甘油三酯水平降低而朝向正常水平降低。尽管他们的代谢模式非常不同，但在甘油三酯或胆固醇水平、极低密度脂蛋白组成或电泳或等电聚焦模式方面，2个高甘油三酯血症组之间没有一致的差异。所有有心血管疾病记录的高胆固醇血症受试者均显示细胞-血浆固醇转运逆转，所有无此类疾病的受试者均显示细胞-血浆固醇转运方向正常。本研究的结果表明，在几组具有遗传上不同的高脂血症的受试者中，血浆胆固醇代谢存在重大且可重复的异常，这些受试者面临动脉粥样硬化血管疾病的风险。胆固醇代谢测量在心血管分析中的可能预测价值进行了讨论。
Cholesterol esterification, cholesteryl ester transfer between lipoproteins and cholesterol transport between lipoproteins and cultured cells were measured in the plasma of 22 patients with primary hyperlipidema and 10 normolipidemic subjects. In hyperbetalipoproteinemia, increase in plasma low density lipoprotein levels was associated with a reduction of cholesteryl ester transfer rates, and with a reveral of the normal direction of sterol transport between fibroblasts and their plasma culture medium. Instead of net transport from cells to medium there was a net uptake of sterol from plasma by the cells, despite a level of plasma lecithin/cholesterol acyltransferase activity that was within the normal range. In dysbetalipoproteinemia, esterification rates were increased above normal levels, but cholesteryl ester transfer was reduced and the direction of sterol transport between the cells and plasma medium was reversed, as in the hyperbetalipoproteinemic group. In hypertriglyceridemia, those subjects with cardiovascular disease showed a metabolic pattern similar to the hyperbetalipoproteinemic group. The subjects in this group without symptoms of cardiovascular disease showed a normal direction of sterol transport, normal or raised rates of cholesteryl ester transfer between lipoproteins, and an increased rate of sterol esterification in plasma that decreased towards normal levels as plasma triglyceride levels decreased. Despite their quite distinct metabolic patterns there was no consistent difference between the 2 hypertriglyceridemic groups in triglyceride or cholesterol levels, very low density lipoprotein composition, or electrophoretic or isoelectric focusing patterns. All hypertriglyceridemic subjects with documented cardiovascular disease showed reversed cell-plasma sterol transport and all subjects without such disease showed a normal direction of cell-plasma sterol transport. The results of this study indicate major and reproducible abnormalities in plasma cholesterol metabolism in several groups of subjects with genetically distinct hyperlipidemias, who are at risk for atherosclerotic vascular disease. The possible predictive value of sterol metabolic measurements in the analysis of cardiovascular is discussed.