Effects of remnant lipoproteins on functions of endothelial cells, smooth muscle

富含甘油三酯的脂蛋白被认为会导致动脉粥样硬化，但确切的机制仍不清楚。因此，我们确定了来自极低密度脂蛋白和乳糜粒的残余脂蛋白是否与人类冠状动脉内皮依赖性血管运动功能异常有显著关系，内皮依赖性血管运动功能异常是动脉粥样硬化的早期迹象。用含抗apoA-1和抗apoB-100单抗的免疫亲和混合凝胶分离剩余脂蛋白。结果表明，残脂蛋白水平与人冠状动脉内皮细胞依赖的血管运动功能异常独立相关，提示残脂蛋白可能损害人冠状动脉内皮细胞的血管运动功能。此外，我们发现口服维生素E(VE)，一种抗氧化剂，改善了残留水平高的患者内皮依赖性血管扩张的损害。因此，氧化应激的增加可能至少部分导致残留水平高的患者的内皮血管运动功能障碍。体外实验表明，残余脂蛋白的抑制作用是不依赖于载脂蛋白的，而且残余脂蛋白中的脂类似乎参与了抑制作用。此外，残余脂蛋白可引起培养内皮细胞的氧化应激，与抗氧化剂共同孵育可抑制残余脂蛋白引起的兔离体主动脉内皮依赖性舒张功能的损伤。总而言之，残余脂蛋白会损害人类冠状动脉的内皮血管运动功能。氧化应激增加可能至少部分导致残留脂蛋白水平高的患者的内皮血管舒缩功能障碍。

Triglycerides-rich lipoproteins are considered atherogenic, but precise mechanisms remain unknown. Thus, we determined whether remnant lipoproteins, derived from very low-density lipoproteins and chylomicrons, may have a significant relation with the abnormal endothelium-dependent vasomotor functions, an early sign with atherosclerotic arteries, in human coronary arteries. The remnant lipoproteins were isolated with the immunoaffinity mixed gel containing anti apoA-1 and anti apoB-100 monoclonal antibodies. The results showed that remnant lipoproteins levels were independently associated with the abnormal endothelium-dependent vasomotor functions in large and resistance coronary arteries in humans, indicating that remnant lipoproteins may impair endothelial vasomotor functions in human coronary arteries. Further, we found that oral intake of vitamin E (VE), an antioxidant, improved impairment of endothelium-dependent vasodilation in patients with high remnants levels. Thus, the increase in oxidative stress may at least partly contribute to endothelial vasomotor dysfunction in patients with high remnants levels. In vitro experiments using isolated rabbits aortas showed that the inhibitory effects of remnant lipoproteins were in apoprotein-independent manner and that the lipids in the remnants seemed to contribute to the inhibitory effects. Furthermore, remnant lipoproteins caused oxidative stress in cultured endothelial cells and the co-incubation with antioxidants suppressed the remnants-induced impairment of endothelium-dependent relaxation of isolated rabbits aortas. Taken together, remnant lipoproteins impair endothelial vasomotor functions in human coronary arteries. The increase in oxidative stress may at least partly contribute to endothelial vasomotor dysfunction in patients with high remnant lipoproteins levels.