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Prevention of atherosclerotic plaque rupture by the regulation of oxygen radical metabolism of vascular wall cells.

Research Project

Project/Area Number 10557071
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Circulatory organs internal medicine
Research InstitutionOsaka University

Principal Investigator

HORI Masatsugu  Graduate School of Medicine, Osaka University, Professor, 医学系研究科, 教授 (20124779)

Co-Investigator(Kenkyū-buntansha) NISHIDA Masashi  Graduate School of Medicine, Osaka University, Assistant Professor, 医学系研究科, 助手 (40283783)
KITAKAZE Masafumi  Graduate School of Medicine, Osaka University, Assistant Professor, 医学系研究科, 助手 (20294069)
KUZUYA Tsunehiko  Graduate School of Medicine, Osaka University, Associate Professor, 医学系研究科, 助教授 (80150340)
TOYOFUKU Toshihiko  Graduate School of Medicine, Osaka University, Assistant Professor, 医学系研究科, 助手
OHTSU Kin-ya  Graduate School of Medicine, Osaka University, Assistant Professor, 医学系研究科, 助手 (20294051)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 1999: ¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 1998: ¥7,700,000 (Direct Cost: ¥7,700,000)
KeywordsAcute Coronary Syndrome / Oxidative Stress / Mn-SOD / Inflammation / 血管平滑筋細胞 / プレコンディショニング / 温熱負荷 / TNF-α / 細胞障害
Research Abstract

Recent studies revealed that myocardial infarction is not occurred from highly progressive atherosclerotic lesions, but rather from relatively mild lesions. Therefore, prevention of rupture of unstable coronary plaque is necessary for the prevention of acute myocardial infarction. In this study, we examined whether regulation of oxygen radical in vascular smooth muscle cells can modulate stability of atherosclerotic plaque. In the first year, we demonstrated that antioxidative enzyme, Mn-SOS, was induced in cultured vascular smooth muscle cells by the preconditioning with heat shock or TNF-α together with the acquisition of tolerance to oxidative stress. In the second year, we revealed that the induction of Mn-SOD by TNF-α was inhibited by the addition of antisenseoligodeoxyribonucleotide (AODN) to Mn-SOD and that the tolerance to oxidative stress was also abolished by the treatment with AODN. On the other hand, lipofection of Mn-SOD to smooth muscle cells introduced Mn-SOD in mitochondria of cells and augmented tolerance to oxidative stress. These results suggest that the expression of antioxidative enzyme in vascular wall cells is closely related to the survival of smooth muscle cells and that by introducing antioxidative enzyme in cells could stabilize atherosclerotic plaque.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Hoshida S, Yamashita N, Otsu K, et al.: "Cholesterol feeding exacerbates myocardial injury in Zucker diabetic fatty rats"Am J. Physiol. Heart Circ. Physiol.. 278. H256-H262 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ueda Y, Kitakaze M, Komamura K, et al.: "Pravastatin restored the infarct size-limiting effect of ischemic preconditioning blunted by hypercholesterolemia in the rabbit model of myocardial infarction"J. Am Coll Cardiol.. 34. 2120-2125 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kitakaze M, Funaya H, Komamura K, et al.: "Nisoldipine selectively induces coronary vasodilation and improves mild myocardial ischemia in dogs : a potential role of cellular acidosis"Cardiovasc Drugs Ther. 12. 533-541 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ueda Y, Kitakaze M, Imakita H, et al.: "Glycoprotein Iib/IIIA antagonist FK633 could not prevent neointimal thicking in stent implantation model of canine coronary artery"Arterioscler. Thromb Vasc Biol.. 19. 343-347 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kitakaze M, Node K, Minamino T, et al.: "A Ca Channel blocker, benidipine , increases coronary blood flow and attenuates the severity of microcardial ischemia via NO-dependent mechanisms in dogs"J. Am Coll Cardiol.. 33. 242-249 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kitakaze M, Node K, Minamino T, et al.: "Inhibition of angiotensine-converting enzyme increases the nitric oxide levels in canine ischemic myocardium"J. Mol Cell Cardiol. 30. 2461-2466 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hoshida, S., N. Yamashita, K. Otsu, T et al.: "Cholesterol feeding exacerbates myocardial injury in Zucker diabetic fatty rats."Journal, Volume-Number, Pages Concerned, Year Am. J. Physiol Heart Circ. Physiol. 278. H256-H262 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ueda, Y., M. Kitakaze, K. Komamura et al.: "Pravastatin restored the infarct size-limiting 34 : effect of ischemic preconditioning blunted by hypercholesterolemia in the rabbit model of myocardial infarction."J. Am. Coll. Cardiol.. 2120-2125 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kitakaze, M., H. Funaya, K. Komamura et al.: "Nisoldipine selectively induces coronary vasodilation and improves mild myocardial ischemia in dogs : a potential role of cellular acidosis."Cardiovasc. Drugs Ther.. 12. 533-541 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ueda, Y., M. Kitakaze, M. lmakita. et al.: "Glycoprotein llb/llla antagonist FK633 could not1 prevent neointimal thickening in stent implantation model of canine coronary artery."Arterioscler. Thromb. Vasc. Biol.. 9. 343-347 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kitakaze, M., K. Node, T. Minamino et al.: "A Ca channel blocker, benidipine, increases coronary blood flow and attenuates the severity of myocardial ischemia via NO-dependent mechanisms in dogs."J. Am. Coll. Cardiol.. 33. 242-249 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kitakaze, M., K. Node, T. Minamino et al.: "Inhibition of angiotensin-converting enzyme increases the nitric oxide levels in canine ischemic myocardium."J. Mol. Cell Cardiol.. 30. 2461-2466 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hoshida, S., N. Yamashita et al.: "Amelioration by quinapril of myocardial infarction induced by coronary occlusion/reperfusion in a rabbit model of atherosclerosis : possible mechanisms."Circulation. 99. 434-440 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Minamino, T., M. Kitakaze et al.: "Increased expression of P-selectin on platelets is a risk factor for silent cerebral infarction in patients with atrial fibrillation : role of nitric oxide."Circulation. 98. 1721-1727 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hoshida, S., N. Yamashita et al.: "Reduction in infarct size by chronic amlodipine treatment in cholesterol-fed rabbits."Atherosclerosis. 138. 163-170 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Minamino, T., M. Kitakaze, H. Asanuma: "Endogenous adenosine inhibits P-selectin-dependent formation of coronary thromboemboli during hypoperfusion in dogs."J. Clin. Invest. 101. 1643-1653 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Minamino, T., M. Kitakaze et al.: "Impact of cornary risk factors on contribution of nitric oxide and adenosine to metabolic coronary vasodilation in humans."J. Am. Coll. Cardiol.. 31. 1274-1279 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ueda Y. et al.: "Pravastatin restored the infarct size-limiting effect of ischemic preconditioning blunted by hypercholesterolemia in the rabbit model myocardial infarction"J Am Coll Cardiol. 34. 2120-2125 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ueda Y. et al.: "Glycoprotein IIb/IIa antagonist FK633 could not prevent neointimal thickening in stent implantation model of canine coronary artery"Arterioscler Thromb Vasc Biol. 19. 343-347 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hoshida S et al.: "Amelioration by quinapril of myocardial infarction induced by coronary occlusion/reperfusion in a rabbit model of atherosclerosis"Circulation. 99. 434-440 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yabuki M,et al.: "Involvement of NF-Y in transcriptional regulation of the phospholamban gene." Eur.J.Biochem.258. 744-751 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamashita N,et al.: "A "second window of protection" occurs 24h after ischemic preconditioning in the rat heart." J.Mol.Cell.Cardiol.30. 1181-1189 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamashita N,et al.: "Whole-body hyperthermia provides biphasic cardioprotection against ischemia/reperfusion injury in the rat." Circulation. 98. 1414-1421 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hoshida S,et al.: "Reduction in infarct size by chronic amlodipine treatment in cholesterol-fed rabbits." Atherosclerosis. 138. 163-170 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Toyofuku T,et al.: "Direct association of the gap junction protein connexin-43 with ZO-1 in cardiac myocytes." J.Biol.Chem.273. 12725-12731 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Igarashi J,et al.: "Inducible nitric oxide synthase augments injury elicited by oxidative stress in rat cardiac myocytes." Am.J.Physiol.74. c245-c252 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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