1998 Fiscal Year Final Research Report Summary
Effects of remnant lipoproteins on functions of endothelial cells, smooth muscle
Project/Area Number |
09670730
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Circulatory organs internal medicine
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Research Institution | Kumamoto University |
Principal Investigator |
KUGIYAMA Kiyotaka Kumamoto Univ.School of Med.cells, and macrophages Department of Cardiovascular Medicine, Assistant Professor., 医学部・附属病院, 講師 (00225129)
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Project Period (FY) |
1997 – 1998
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Keywords | Atherosclerosis / Endothelial cells / Lipoproteins / Coronary artery disease / Oxidative stress |
Research Abstract |
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.
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Research Products
(8 results)
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[Publications] Kiyotaka Kugiyama, Hideki Doi, Takeshi Motoyama, Hirofumi Soejima, Kenji Misumi, Hiroaki Kawano, Osamu Nakagawa, Michihiro Yoshimura, Hisao Ogawa, Toshiyuki Matsumura, Seigo Sugiyama, Takamitsu Nakano, Katsuyuki Nakajima, Hirofumi Yasue.: "Association of remnant lipoproteins levels with impairment of endothelium-dependent vasomotor functions in human coronary arteries." Circulation.97. 2519-2526 (1998)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kiyotaka Kugiyama, Takeshi Motoyama, Hiroaki Kawano, Hideki Doi, Nobutaka Hirai, Hirofumi Soejima, Yuji Miyao, Keiji Takazoe, Yasushi Moriyama, Yuji Mizuno, Ryusuke Tsunoda, Seigo Sugiyama, Tomohiro Sakamoto, Hisao Ogawa, Hirofumi Yasue.: "Improvement of endothelium vasomotor dysfunction by treatment with alpha-tocopherol in patients with high remnant lipoproteins levels." J Am Coll Cardiol.(in press). (1999)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Hideki Doi, Kiyotaka Kugiyama, Masamichi Ohgushi, Seigo Sugiyama, Toshiyuki Matsumura, Yasutaka Ohta, Hideki Oka, Nobuhiko Ogata, Akira Hirata, Yorihiro Yamamoto, Hirofumi Yasue: "Membrane active lipids remnant lipoproteins cause impairment of endothelium-dependet vasodilation." Arterioscler Thromb Vasc Biol.( in press). (1999)
Description
「研究成果報告書概要(欧文)」より