Doi H, Kugiyama K, Ohgushi M, Sugiyama S, Matsumura T, Ohta Y, Nakano T, Nakajima K, Yasue H
Division of Cardiology, Kumamoto University School of Medicine, Kumamoto City, Japan.
Atherosclerosis. 1998 Apr;137(2):341-9. doi: 10.1016/s0021-9150(97)00291-8.
Remnants of chylomicron and very low density lipoprotein (VLDL) have been implicated as potentially atherogenic. Since endothelial dysfunction is an early event in atherosclerosis, we examined effects of the remnants on endothelium-dependent vasorelaxation. The remnant lipoproteins were isolated from postprandial plasma in hyperlipidemic subjects using the immunoaffinity gel mixture of anti apo A-1 and anti apo B-100 monoclonal antibodies and ultracentrifugation. Rabbit aortic strips suspended in the organ chambers were incubated for 2 h with the preparations of lipoproteins and lipids. After incubation, the strips were tested with vasodilators after precontraction with phenylephrine (1 microM). The remnant lipoproteins (750-1500 microg triglyceride/ml) but not VLDL fraction (up to 1500 microg triglyceride/ml) impaired vasorelaxation in responses to acetylcholine, substance P and A23187. Carbamylated or methylated remnant lipoproteins, chemically modified remnant lipoproteins, had comparable impairment of the vasorelaxation as unmodified remnant lipoproteins. Incubation with lipid extracts from the remnant lipoproteins also exerted an inhibitory effect on the vasorelaxation. Relaxation to sodium nitroprusside was fully preserved in all aortas exposed to the lipoprotein preparations. Thus, the remnant lipoproteins impair endothelium-dependent arterial relaxation at the concentrations observed in the plasma in patients with coronary artery disease (500-2000 microg triglyceride of remnant lipoprotein/ml). The impairment may be in apoprotein receptor-independent manner, and the lipids in the remnants seem to contribute to the inhibitory effect. The endothelial dysfunction caused by the remnant lipoproteins may play a role in the high prevalence of atherosclerotic coronary artery disease in postprandial hyperlipidemic patients.
乳糜微粒残余物和极低密度脂蛋白（VLDL）被认为具有潜在的致动脉粥样硬化作用。由于内皮功能障碍是动脉粥样硬化的早期事件，我们研究了这些残余物对内皮依赖性血管舒张的影响。使用抗载脂蛋白A-1和抗载脂蛋白B-100单克隆抗体的免疫亲和凝胶混合物和超速离心法，从高脂血症患者的餐后血浆中分离出残余脂蛋白。将悬挂在器官腔室中的兔主动脉条与脂蛋白和脂质制剂孵育2小时。孵育后，在用去氧肾上腺素（1 microM）预收缩后，用血管舒张剂对主动脉条进行测试。残余脂蛋白（750 - 1500微克甘油三酯/毫升）而非VLDL组分（高达1500微克甘油三酯/毫升）会损害对乙酰胆碱、P物质和A23187的血管舒张反应。氨基甲酰化或甲基化的残余脂蛋白，即化学修饰的残余脂蛋白，对血管舒张的损害与未修饰的残余脂蛋白相当。用残余脂蛋白的脂质提取物孵育也对血管舒张产生抑制作用。在所有暴露于脂蛋白制剂的主动脉中，对硝普钠的舒张反应均完全保留。因此，在冠心病患者血浆中观察到的浓度下（残余脂蛋白甘油三酯500 - 2000微克/毫升），残余脂蛋白会损害内皮依赖性动脉舒张。这种损害可能是以不依赖载脂蛋白受体的方式，并且残余物中的脂质似乎促成了这种抑制作用。残余脂蛋白引起的内皮功能障碍可能在餐后高脂血症患者动脉粥样硬化性冠心病的高发病率中起作用。
