Moers A, Fenselau S, Schrezenmeir J
Dpt. Physiology and Biochemistry of Nutrition, Federal Research Centre, Kiel, Germany.
Exp Clin Endocrinol Diabetes. 1997;105 Suppl 2:35-7. doi: 10.1055/s-0029-1211793.
An increased adherence of leukocytes to the vascular endothelium appears to be a crucial event in the development of atherosclerosis. The role of endothelial cell adhesion molecules is gaining increasingly interest in this context. Several studies show an influence of lipoproteins, especially low-density-lipoproteins on adhesion molecule stimulation. The aim of our study was to analyze the atherogenic potential of postprandially elevated serum triglyceride levels by investigating the impact of postprandial lipoproteins (chylomicrons (CH, isolated 4 h after a standard oral lipid load)) on the expression of E-selectin (endothelial leukocyte adhesion molecule-1, ELAM-1) and VCAM-1 (vascular cell adhesion molecule-1). In addition we used chylomicrons that had been incubated with lipoprotein lipase (50 U/ml) for 3 h (CH-LPL). The endotoxin lipopolysaccharide (LPS) served as positive control for adhesion molecule stimulation. Human umbilical vein endothelial cells (HUVEC) were incubated with the samples for 4 h and expression of E-Selectin and VCAM-1 was determined by ELISA. The expression of E-selectin was induced by LPS (530 +/- 64% compared to the basal activity (= 100%)) and by CH (342 +/- 94%); CH-LPL had no effect on E-Selectin expression. VCAM-1 expression was stimulated by LPS (395 +/- 221%) and similarly by CH-LPL (322 +/- 136%) but considerably stronger by CH (1245 +/- 324). In summary, chylomicrons induced an enhancement of the expression of both adhesion molecules, which closely resembled or even exceeded the endotoxin-induced stimulation. Interestingly, this effect was diminished or even reversed after incubation with LPL.
白细胞与血管内皮的粘附增加似乎是动脉粥样硬化发展过程中的一个关键事件。在此背景下,内皮细胞粘附分子的作用越来越受到关注。多项研究表明脂蛋白,尤其是低密度脂蛋白对粘附分子的刺激有影响。我们研究的目的是通过研究餐后脂蛋白(乳糜微粒(CH,标准口服脂质负荷后4小时分离))对E-选择素(内皮白细胞粘附分子-1,ELAM-1)和血管细胞粘附分子-1(VCAM-1)表达的影响,来分析餐后血清甘油三酯水平升高的致动脉粥样硬化潜力。此外,我们使用了与脂蛋白脂肪酶(50 U/ml)孵育3小时的乳糜微粒(CH-LPL)。内毒素脂多糖(LPS)用作粘附分子刺激的阳性对照。将人脐静脉内皮细胞(HUVEC)与样品孵育4小时,并通过ELISA测定E-选择素和VCAM-1的表达。E-选择素的表达由LPS诱导(与基础活性(=100%)相比为530±64%)和CH诱导(342±94%);CH-LPL对E-选择素表达无影响。VCAM-1的表达受到LPS刺激(395±221%),CH-LPL也有类似刺激(322±136%),但CH的刺激作用更强(1245±324)。总之,乳糜微粒诱导了两种粘附分子表达的增强,这与内毒素诱导的刺激非常相似甚至超过了内毒素诱导的刺激。有趣的是,与LPL孵育后,这种作用减弱甚至逆转。