Hughes T A, Elam M B, Applegate W B, Bond M G, Hughes S M, Wang X, Tolley E A, Bittle J B, Stentz F B, Kang E S
Department of Medicine, University of Tennessee, Memphis 38163, USA.
Metabolism. 1995 Aug;44(8):1082-98. doi: 10.1016/0026-0495(95)90108-6.
Three groups of age- and weight-matched men (aged 40 to 70 years) without diabetes were studied: controls (n = 10), plasma triglycerides (TG) less than 180 mg/dL and no cardiovascular disease (CVD); HTG-CVD (n = 11), hypertriglyceridemic (HTG) (TG > 240 mg/dL) without CVD; and HTG+CVD (n = 10), HTG (TG > 240 mg/dL) with documented CVD. HTG+CVD subjects had higher fasting and post-oral glucose tolerance test insulin levels than the other two groups, respectively. Very-low-density lipoprotein (VLDL)+chylomicrons (CMs), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), and three high-density lipoprotein (HDL) subfractions (HDL-L, HDL-M, and HDL-D, from least to most dense) were isolated by gradient ultracentrifugation. Fasting lipoproteins were similar in HTG groups, except for higher VLDL lipid to apolipoprotein (apo) B ratios (P < .04) in the HTG+CVD group. Subjects were fed a high-fat mixed meal, and lipoprotein composition was determined at 3, 6, 9, and 12 hours postprandially. Postprandial responses of the core lipids (TG and cholesterol esters [CE]) in all of the lipoprotein subfractions were similar in the two HTG groups at each time point. However, both controls and HTG-CVD subjects had increases in HDL-M phospholipid (PL) at 9 and 12 hours with no change in HDL-D PL. The HTG+CVD group, on the other hand, had no increase in HDL-M PL and had a substantial reduction in HDL-D PL. These changes resulted in significant increases in HDL-M and HDL-D PL to apo A-I ratios in both controls and HTG-CVD subjects between 6 and 12 hours, whereas there was no increase seen in the HTG+CVD group. The HTG-CVD group also had a significantly greater increase in the VLDL+CM PL to apo B ratio (P = .038) at 3 hours than the HTG+CVD group. This diminished amount of surface lipid per VLDL particle may account for the late decrease in the HDL-D PL to apo A-I ratio seen in HTG+CVD patients. There were no other postprandial lipid or apolipoprotein differences between the two HTG groups. We conclude therefore that the major postprandial lipoprotein abnormality in these HTG+CVD patients was a failure to increase the PL content per particle in VLDL+CM, HDL-M, and HDL-D. This abnormality could prevent the usual increase in reverse cholesterol transport seen in postprandial plasma and therefore contribute to their increased incidence of CVD. The greater insulin resistance seen in these patients also appears to contribute significantly to their CVD.
研究了三组年龄和体重匹配的无糖尿病男性（年龄40至70岁）：对照组（n = 10），血浆甘油三酯（TG）低于180 mg/dL且无心血管疾病（CVD）；高甘油三酯血症无心血管疾病组（HTG-CVD，n = 11），高甘油三酯血症（HTG）（TG > 240 mg/dL）且无CVD；高甘油三酯血症合并心血管疾病组（HTG+CVD，n = 10），HTG（TG > 240 mg/dL）且有记录的CVD。HTG+CVD组受试者的空腹和口服葡萄糖耐量试验后胰岛素水平分别高于其他两组。通过梯度超速离心分离极低密度脂蛋白（VLDL）+乳糜微粒（CM）、中间密度脂蛋白（IDL）、低密度脂蛋白（LDL）以及三种高密度脂蛋白（HDL）亚组分（HDL-L、HDL-M和HDL-D，密度由低到高）。HTG组的空腹脂蛋白相似，但HTG+CVD组的VLDL脂质与载脂蛋白（apo）B比率更高（P <.04）。给受试者喂食高脂混合餐，并在餐后3、6、9和12小时测定脂蛋白组成。在每个时间点，两个HTG组中所有脂蛋白亚组分的核心脂质（TG和胆固醇酯[CE]）的餐后反应相似。然而，对照组和HTG-CVD组受试者在9和12小时时HDL-M磷脂（PL）增加，而HDL-D PL无变化。另一方面，HTG+CVD组HDL-M PL未增加，且HDL-D PL大幅降低。这些变化导致对照组和HTG-CVD组在6至12小时之间HDL-M和HDL-D PL与apo A-I比率显著增加，而HTG+CVD组未见增加。HTG-CVD组在3小时时VLDL+CM PL与apo B比率的增加也显著大于HTG+CVD组（P = 0.038）。每个VLDL颗粒表面脂质数量的减少可能解释了HTG+CVD患者中HDL-D PL与apo A-I比率后期的降低。两个HTG组之间餐后脂质或载脂蛋白无其他差异。因此，我们得出结论，这些HTG+CVD患者主要的餐后脂蛋白异常是VLDL+CM、HDL-M和HDL-D中每个颗粒的PL含量未能增加。这种异常可能会阻止餐后血浆中通常出现的逆向胆固醇转运增加，因此导致他们CVD发病率升高。这些患者中较高的胰岛素抵抗似乎也对他们的CVD有显著影响。
