Karpe F, Tornvall P, Olivecrona T, Steiner G, Carlson L A, Hamsten A
King Gustaf V Research Institute, Karolinska Hospital, Stockholm, Sweden.
Atherosclerosis. 1993 Jan 4;98(1):33-49. doi: 10.1016/0021-9150(93)90221-f.
A preponderance of small, dense low density lipoprotein (LDL) particles has been linked to increased risk of myocardial infarction, and a dense and protein-rich LDL has proved to be a characteristic of patients with manifest coronary heart disease (CHD). The present study focused on metabolic determinants of the LDL subfraction distribution with the emphasis placed on alimentary lipaemia. The relations of plasma levels and composition of light (1.019 < d < 1.040 kg/l) and dense (1.040 < d < 1.063 kg/l) LDL subfractions to postprandial triglyceride-rich lipoproteins (TGRL), postheparin plasma lipase activities and the activity of cholesteryl ester transfer protein (CETP) were studied in 32 men with angiographically ascertained premature coronary atherosclerosis (age 48.8 +/- 3.2 years) and in 10 age matched healthy control men. LDL subfractions were separated by equilibrium density gradient ultracentrifugation of fasting plasma drawn before participants were subjected to an oral fat tolerance test of a mixed meal type. The response of TGRL to the oral fat load was determined by measuring plasma triglycerides, and the apolipoprotein (apo) B-48 and apo B-100 content of Sf 60-400 and Sf 20-60 lipoprotein fractions. At a second visit plasma samples were taken for determination of postheparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities and for measurement of CETP activity. Hypertriglyceridaemic patients had a preponderance of dense LDL particles compared with normotriglyceridaemic patients and controls. The magnitude of the response of TGRL to the oral fat load showed a positive association with the dense LDL apo B concentration (r = 0.32-0.52, P < 0.05), whereas the LPL activity correlated positively with the free (r = 0.50, P < 0.001) and esterified cholesterol (r = 0.45, P < 0.01) and apo B (r = 0.42, P < 0.01) content of the light LDL fraction. The HL activity was found to be inversely associated with the plasma level of light LDL triglycerides (r = -0.38, P < 0.05). In contrast, no relations were noted between CETP activity and plasma concentrations of LDL constituents. Multiple stepwise linear regression analysis with the proportion of total LDL apo B contained in the dense LDL subfraction (% dense LDL apo B) used as the dependent variable indicated that the combined effect of LPL activity and postprandial plasma levels of TGRL (areas under the curve for plasma triglycerides or Sf 60-400 apo B-48) accounted for around 50% of the variability in the distribution of LDL particles between light and dense subfractions.(ABSTRACT TRUNCATED AT 400 WORDS)
大量小而致密的低密度脂蛋白(LDL)颗粒与心肌梗死风险增加有关,事实证明,致密且富含蛋白质的LDL是显性冠心病(CHD)患者的一个特征。本研究聚焦于LDL亚组分分布的代谢决定因素,重点是饮食性脂血症。在32名经血管造影确诊为早发性冠状动脉粥样硬化的男性(年龄48.8±3.2岁)和10名年龄匹配的健康对照男性中,研究了轻密度(1.019<d<1.040 kg/l)和高密度(1.040<d<1.063 kg/l)LDL亚组分的血浆水平和组成与餐后富含甘油三酯脂蛋白(TGRL)、肝素后血浆脂肪酶活性及胆固醇酯转移蛋白(CETP)活性之间的关系。在参与者接受混合餐型口服脂肪耐量试验前,通过对空腹血浆进行平衡密度梯度超速离心来分离LDL亚组分。通过测量血浆甘油三酯以及Sf 60 - 400和Sf 20 - 60脂蛋白组分中的载脂蛋白(apo)B - 48和apo B - 100含量,来确定TGRL对口服脂肪负荷的反应。在第二次就诊时采集血浆样本,用于测定肝素后血浆脂蛋白脂肪酶(LPL)和肝脂肪酶(HL)活性以及CETP活性。与正常甘油三酯血症患者和对照组相比,高甘油三酯血症患者的致密LDL颗粒占优势。TGRL对口服脂肪负荷的反应程度与致密LDL apo B浓度呈正相关(r = 0.32 - 0.52,P<0.05),而LPL活性与轻密度LDL组分的游离胆固醇(r = 0.50,P<0.001)、酯化胆固醇(r = 0.45,P<0.01)和apo B(r = 0.42,P<0.01)含量呈正相关。发现HL活性与轻密度LDL甘油三酯的血浆水平呈负相关(r = -0.38,P<0.05)。相比之下,未发现CETP活性与LDL成分的血浆浓度之间存在关联。以高密度LDL亚组分中总LDL apo B的比例(%致密LDL apo B)作为因变量进行多元逐步线性回归分析表明,LPL活性和餐后血浆TGRL水平(血浆甘油三酯或Sf 60 - 400 apo B - 48的曲线下面积)的联合作用约占轻密度和高密度亚组分之间LDL颗粒分布变异性的50%。(摘要截选至400字)