|Budget Amount *help
¥3,200,000 (Direct Cost : ¥3,200,000)
Fiscal Year 1998 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 1997 : ¥2,300,000 (Direct Cost : ¥2,300,000)
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.