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

富含甘油三酯的脂蛋白被认为是致动脉粥样硬化的，但确切的机制仍然未知。因此，我们确定是否残余的脂蛋白，来自极低密度脂蛋白和乳糜微粒，可能有显着的关系，异常内皮依赖性血管功能，动脉粥样硬化的早期迹象，在人冠状动脉。用含抗apoA-1和抗apoB-100单克隆抗体的免疫亲和混合胶分离残余脂蛋白。结果表明，残余脂蛋白水平与人大动脉和阻力冠状动脉内皮依赖性血管功能异常独立相关，表明残余脂蛋白可能损害人冠状动脉内皮功能。此外，我们发现，口服维生素E（VE），一种抗氧化剂，改善高残留水平患者的内皮依赖性血管舒张功能受损。因此，氧化应激的增加可能至少部分导致高残留物水平患者的内皮血管功能障碍。离体实验表明，残余脂蛋白的抑制作用不依赖于载脂蛋白，残余物中的脂质可能参与抑制作用。此外，残余的脂蛋白引起的氧化应激在培养的内皮细胞和共孵育的抗氧化剂抑制残余物诱导的损伤的内皮依赖性舒张的离体兔髂动脉。总之，残余脂蛋白损害人冠状动脉内皮血管功能。在高残余脂蛋白水平的患者中，氧化应激的增加可能至少部分导致内皮血管功能障碍。

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.