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

Research Project

Project/Area Number 09670730
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionKumamoto 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)

Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
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)
KeywordsAtherosclerosis / 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.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Kiyotaka Kugiyama: "Intracoronary infusion of reduced glutathione improves endothelial vasomotor response to acetylcholine in human coronary circulation" Circulation. 97. 2299-2301 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takeshi Motoyama: "Vitamin E Administration improves impairment of endothelium-dependent vasodilation in patients with coronary spastic angina" J Am Coll Cardiol. 32. 1672-1679 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hideki Doi: "Membrane active lipids in remnant lipoproteins cause impairment of endothelium-dependent vasodilation" Arteriosclerosis, Thrombosis, and Vascular Biology. (in press). (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kiyotaka Kugiyama: "Improvement of endothelial 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(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hideki Doi, Kiyotaka Kugiyama, Masamichi Ohgushi, Seigo Sugiyama, Toshiyuki Matsumura, Yasutaka Ohta, Takamitsu Nakano, Katsuyuki Nakajima, Hirofumi Yasue.: "Remnants of chylomicron and very low density lipoprotein impair endothelium-dependent vasorelaxation." Atherosclerosis. 137. 341-349 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kiyotaka Kugiyama: "Intracoronary infusion of reduced glutathione improves endothelial vasomotor response to acetylcholine in human coronary circulation" Circulation. 97. 2299-2301 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takashi Motoyama: "Vitamin E administration improves impairment of endothelium-dependent vasodilation in patients with coronary spastic angina" J Am Coll Cardiol. 32. 1672-1679 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hideki Doi: "Membrane active lipids in remnant lipoproteins cause impairment of endothelium-dependent vasodilation" Arteriosclerosis,Thrombosis,and Vascular Biology. in press. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kiyotaka Kugiyama: "Improvement of endothelial vasomotor dysfunction by treatment with alpha-tocopherol in patients with high remnant lipoproteins levels" J Am Coll Cardiol. in press. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kiyotaka Kugiyama,: "Supersensitive dilator response to nitroglycerin but not to atrial natriuretic peptide in spasm coronary arteries in patients with coronary spastic angina." Am J Cardiol. 79. 606-610 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kiyotaka Kugiyama,: "Nitric oxide-mediated flow-dependent dilation is impaired in coronary arteries in patients with coronary spastic angina." J Am Coll Cardiol. 30. 920-926 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kiyotaka Kugiyama,: "Comparison of coronary hemodynamics during infusions of dobutamine and adenosine in patients with angina pectrois." Jpn Cire J. 62. 1-6 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kiyotaka Kugiyama,: "Association of remnant lipoproteins livels with impairment of endothelium-dependent vasomotor functions in human coronary arteries" Circulation. (in press). (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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