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Roles of oxidatively modified lipoproteins in atherogenesis

Research Project

Project/Area Number 03454251
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Circulatory organs internal medicine
Research InstitutionNagoya University

Principal Investigator

ASAI Kanichi (1992-1993)  Nagoya University, School of Medicine Assistant Prof., 医学部, 講師 (70151008)

葛谷 文男 (1991)  名古屋大学, 医学部, 教授 (80023761)

Co-Investigator(Kenkyū-buntansha) YOSHIMINE Noboru  Nagoya University, School of Medicine Associate Prof., 医学部, 助教授 (40022842)
NAITO Michitaka  Nagoya University, School of Medicine Research Associate, 医学部, 助手 (10198012)
浅井 幹一  名古屋大学, 医学部, 講師 (70151008)
Project Period (FY) 1991 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 1993: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1992: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1991: ¥2,900,000 (Direct Cost: ¥2,900,000)
Keywordsatherogenesis / endothelial cell / oxidatively modified lipoprotein / lipid hydroperoxide / copper ion / cytotoxity / endothelium-dependent relaxation / lysolecithin / 血管内皮 / 細胞障害性 / マクロファージ
Research Abstract

We studied the mechanism of the toxicity of oxidatively-modified LDL (oxLDL) modified by the presence of copper or iron against cultured bovine aortic endothelial cells. The cytotoxicity of the substances produced by the oxidation of LDL are present in oxLDL particles, but not in the apueous phase. The binding of copper ions to the oxLDL particle is required to induce toxicity in endothelial cells. The toxicity of oxLDL depends on the levels of LPO and not on the TBARS content, the extent of the negative charge, or the protein adduct of aldehydes, suggesting that lipid hydroperoxides associated with the oxLDL particle constitute the toxic moiety of oxLDL.And the lipid hydroperoxides may generate hydroxyl and alkoxyl radicals in the presence of iron, probably supplied by intracellular iron stores in endothelial cells and exhibit toxicity to the cells. And the impairment of endothelium-dependent relaxation of swine coronary artery by oxLDL is also related to both LPO and copper ion associated with the lipoptotein particle.

Report

(4 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • 1991 Annual Research Report
  • Research Products

    (39 results)

All Other

All Publications (39 results)

  • [Publications] 内藤通孝・井口昭久: "老化と変性脂質" 現代医療. 26(印刷中). (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Naito M,Kuzuya M,Iguchi A.: "Mechanisms of endothelial injury induced by oxidatively modified LDL" J.Jpn Atheroscler Soc. 22(印刷中). (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 内藤通孝,林登志雄: "動脈硬化性疾患診療上の問題点-動脈硬化性疾患の危険因子としてのfibrinogen" 日本老年医学会誌. 31(印刷中). (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Naito M,Hayashi T,Yamada K,Asai K,Yoshimine N,Iguchi A.: "Protective effects of idebenoneon vascular endothelial cells against toxicity induced by oxidatively modified low density lipoprotein" Artery. 20(印刷中). (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kuzuya M,Naito M.: "Probucol prevents oxidative injury to endotherial cells" J.Lipid Res.32. 197-204 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kuzuya M,Naito M.: "Lipid peroxide and transition metals are requid for the toxicity of oxidized lipoprotein to cultured endotherial cells" Biochim.Biophys.Acta. 1096. 155-161 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kuzuya M,Yamada K.: "Oxidation of low-density lipoprotein by copper and iron in phosphate buffer" Biochim.Biophys.Acta. 1084. 198-201 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kuzuya M,Yamada K.: "Role of lipoprotein-copper complex in copper-catalyzed peroxidation of low-density lipoprotein" Biochim.Biophys.Acta. 1123. 334-341 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yamada K,Naito M.: "Effects of dexamethasone on migration of human monocytes in response to oxidized β-very low density lipoprotein" Artery. 20. 253-267 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Naito M,Yamada K.: "Oxygen Radicals" Elsevier Science Publishers, 373-376 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kazuya M, Naito M, Funaki C, Hayashi T, Asai K, Kazuya F: "Probucol prevents oxidative injury to endothelial cells" J Lipid Res. 32. 197-204 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kazuya M, Naito M, Funaki C, Hayashi T, Asai K, Kazuya F: "Lipid peroxide and transition metals are required for the toxicity of oxidized low density lipoprotein to cultured endothelial cells." Biochim Biophys Acta. 1096. 155-161 (0991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kazuya M, Yamada K, Hayashi T, Funaki C, Naito M, Asai K, Kazuya F: "Oxidation of low-denscity lipoprotein by copper and iron in phosphate buffer." Biochim Biophys Acta. 1084. 198-201 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kazuya M, Yamada K, Hayashi T, Funaki C, Naito M, Asai K, Kazuya F: "Role of lipoprotein-copper complex in copper catalyzed-peroxidation of low-density lipoprotein" Biochim Biophys Acta. 1123. 334-341 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Naito M, Yamada K, Funaki C, Asai K, Yoshimine N, Kazuya F: "Mechanism of oxidatively-modified low density lipoprotein toxicity to cultured vascular endothelial cells. Comparison with lysophosphatidylcholine." In Oxygen Radicals. 373-376 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Naito M, Hayashi T, Yamada K, Asai K, Yoshimine N, Iguchi A.: "Protective effects of idebenone on vascular endothelial cells against toxicity induced by oxidatively modified low density lipoprotein." Artery. (In press). (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yamada K, Naito M, Hayashi T, Asai K, Yoshimine N, Iguchi A.: "Effects of dexamethasone on migration of human monocyts in response to oxidezed beta-very low density lipoprotein." Artery. 20. 253-267 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kazuya M, Kazuya F: "Probucol as an antioxidant and antiatherogenic drug" Free Rad Biol Med. 14. 67-77 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 内藤通孝、井口昭久: "臓器障害と酸素ストレス,血管障害" Medical Immunology. 26. 531-539 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Naito M,Kuzuya F.: "Effects of calcium antagonists and other antihypertensive agents on experimental atherosclerosis:a review" J.Clin Biochem.Nutr.15. 77-90 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Asai K,Funaki C.: "Dexamethasone-induced suppression of aortic atherosclerosis in cholesterol-fed rabbits" Arteriosclerosis Thromb.13. 892-899 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Asai K,Kawahara H.: "Hemodialysis and the elderly patient:Retrospective analysis of morbidity and mortality" Geriatric Nephrology and Urology. 3. 139-144 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yoshimine N: "Effects of exercise testing on lipid peroxide levels of plasma and erythrocyte ghosts" J.Clin.Biochem.Nutr.15. 51-56 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yamada K,Naito M.: "Effects of dexamethasone on migration of human monocytes in response to oxidized β-very low density lipoprotein" Artery. 20. 253-267 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kuzuya M,Kuzuya F.: "Probucol as an antioxidant and antiatherogenic drug" Free Rad.Biol.Med.14. 67-77 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Naito M,Hayashi T.: "Protective effects of idebenone on vascular endotherial cells against toxicity induced by oxidatively modified low density lipoprotein" Artery. 20(印刷中). (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Naito M,Kuzuya M.: "Mechanism of endotherial injury induced by oxidatively modified LDL" J.Jpn Atheroscler.Soc.22(印刷中).

    • Related Report
      1993 Annual Research Report
  • [Publications] 内藤通孝.井口昭久: "老化と変性脂質" 現代医療. 26(印刷中). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 内藤通孝、林登志雄: "動脈硬化性疾患診療上の問題点-動脈硬化性疾患の危険因子としてのfibrinogen" 日本老年医学会誌. 31(印刷中). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Michitaka Naito,Kazuyoshi Yamada,Chiaki Funaki,Kanichi Asai,Noboru Yoshimine,and Fumio Kuzuya: "Mechanism of oxidatively-modified low density lipoprotein toxicity to cultured vascular endothelial Cells.Comparison with lysophosphatidylcholine" Oxygen Radicals. 373-376 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Michitaka Naito,Chiaki Funaki,Toshio Hayashi,Kazuyoshi Yamada,Kanichi Asai,Noboru Yoshimine,and Fumio Kuzuya: "Substrate-bound fibrinogen,fibrin and other cell attachment-promoting proteins as ascaffold for cultured vascular smooth muscle cells" Atherosclerosis. Vol.96. 227-234 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Toshio Hayashi,Jon M.Fukuto,Louis J.Ignarro,and Gautam Chaudhuri: "Basal release of nitric oxide from aortic rings is greater in female rabbits than in male rabbits:Implications for atherosclerosis" Proc.Natl.Acad.Sci.USA. Vol.89. 11259-11263 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Toshio Hayashi,Noboru Yoshimine,Michitaka Naito,Chiaki Funaki Kazuyoshi Yamada,Kanichi Asai,and Fumio Kuzuya: "HDL DOES NOT PROMOTE CHOLESTEROL EFFLUX FROM MACROPHAGES OF HYPERCHOLESTROLEMIC RABBIT:EFFLUX DIFFERENCES BETWEEN SPECEES" ARTERY. 19(4). 184-198 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 葛谷 文男,内藤 通孝,葛谷 雅文: "老化と動脈硬化ー最近の知見を中心にー" 老化と疾患. 5. 183-194 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] 内藤 通孝,葛谷 文男: "酸化変性LDL銅依存性LDLの生成" 活性酸素・フリ-ラジカル. 2. 440-451 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Kuzuya M,Naito M,Funaki C,Hayashi T,Asai K,Kuzuya F.: "Probucol prevents oxidative injury to endothelial cells" J Lipid Res. 32. 197-204 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Kuzuya M,Naito M,Funaki C,Hayashi T,Asai K,Kuzuya F: "Lipid peroxide and transition metals are required for the toxicity of oxidized low density lipoprotein to cultured endothelial cells." Biochim Biophys Acta. 1096. 155-161 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Kuzuya M,Yamada K,Hayashi T,Funaki C,Naito M,Asai K,Kuzuya F: "Oxidation of lowーdensity lipoprotein by copper and iron in phosphate buffer" Biochim.Biophys Acta. 1084. 198-201 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Naito M,Yamada K,Funaki C,Asai K,Yoshimine N,Kazuya F: "Mechanism of oxidativelyーmodified low density lipoprotein toxicity to cultured vascular endothelial cells.Comparison with Iysophosphatidylcholine.In the Proceedings of 5ICOR" 5th International Congress on Oxygen Radicals, (1992)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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