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Cross talk of oxidative and chronic mental stress in pathogenesis of coronary artery disease.

Research Project

Project/Area Number 13670712
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionKobe University

Principal Investigator

INOUE Nobutaka  Kobe University Graduate School of Medicine, Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Assistant Professor, 大学院・医学系研究科, 助手 (10304099)

Co-Investigator(Kenkyū-buntansha) KAWASHIMA Seinosuke  Kobe University Graduate School of Medicine, Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (10177678)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsNADH / NADPH oxidase / Coronary artery disease / SOD / Unstable plaque / thioredoxin / 酸化ストレス / 精神的ストレス / NADH / NADPH oxidase / 動脈硬化
Research Abstract

[Background] Oxidative stress induced by reactive oxygen species (ROS) plays an important role in pathogenesis of ischemic heart disease. The redox state is determined by the balance between antioxidants and the ROS generating system. Against enhanced ROS, mammalian cells have a complex network of antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase. On the other hand, NAD (P) H oxidase is a major source of ROS in vascular cells. [Purpose] To clarify the role of oxidative stress in atherosclerotic vascular diseases, we investigated by immunohistoshemistry the expressional changes of antioxidative enzymes and NAD (P) H oxidase in coronary arteries specimens obtained from autopsied cases and directional coronary atherectomy (DCA). Furthermore, the influence of chronic mental stress on the redox state was examined using rat restrain-models. [Results] In nonatherosclerotic coronary arteries, Cu/Zn SOD and Mn SOD were expressed in medial smooth muscle cells (SMC), whereas cytosolic GPx (GPx-1) was expressed mainly in endothelium and weakly in medial SMC. Migrating SMCs and macrophages in atheromatous plaques expressed these antioxidative enzymes intensively. The generation of ROS in DCA specimens were closely associated with the distribution of NADH/NADPH oxidase p22^<phox> and oxidized LDL. There was a correlation between ROS and the expression of p22^<phox> or oxidized LDL. Chronic mental stress enhanced in vascular ROS generation in rat restrain-models. [Conclusion] The expression of antioxidant enzymes and the ROS generating system are dynamically regulated. Chronic mental stress induced their imbalance.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report

Research Products

(53 results)

All Other

All Publications (53 results)

  • [Publications] Yamashita T: "Role of endogenous nitric oxide generation in the regulation of vascular tone and reactivity in small vessels as investigated in transgenic mice using synchrotron radiation micro angiography"Nitric Oxide. 5(5). 494-503 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okuda M: "Expression of glutaredoxin in human coronary arteries : its potential role in antioxidant protection against atherosclerosis"Arterioscler Thromb Vase Biol.. 21(9). 1483-1484 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawashima S: "Endothelial NO synthase overexpression inhibits lesion formation in mouse model of vascular remodeling"Arterioscler Thromb Vase Biol.. 21(2). 201-207 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Seno T: "Involvement of NADH/NADPH oxidase in human platelet ROS production"Thromb Res.. 103(5). 399-409 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Rikitake Y: "Anti-oxidative properties of fluvastatin, an HMG-CoA reductase inhibitor, contribute to prevention of atherosclerosis in cholesterol-fed rabbits"Atheroselerosis. 154(1). 87-96 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Inoue N: "Lysophosphatidylcholine increases the secretion of matrix metalloproteinase 2 through the activation of NADH/NADPH oxidase in cultured aortic endothelial cells"Atherosclerosis. 155(1). 45-52 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Rikitake Y: "Regulation of tyrosine phosphorylation of PYK2 in vascular endothelial cells by lysophosphatidylcholine"Am J Physiol Heart Circ Physiol.. 281(1). H266-H274 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Rikitake Y: "Signaling mechanism underlying COX-2 induction by lysophosphatidylcholine"Biochem Biophys Res Commun.. 281(5). 1291-1297 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Rikitake Y: "Involvement of endothelial nitric oxide in sphingosine-1-phosphate-induced angiogenesis"Arterioscler Thromb Vasc Biol.. 22(1). 108-114 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sumi Y: "Expression of tissue transglutaminase and elafin in human coronary artery. Implication for plaque instability"Atherosclerosis. 160(1). 31-39 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Rikitake Y: "Expression of G2A, a receptor for lysophosphatidylcholine, by macrophages in murine, rabbit, and human atherosclerotic plaques"Arterioscler Thromb Vasc Biol.. 22(12). 157-163 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ozaki M: "Overexpression of endothelial nitric oxide synthase accelerates atherosclerotic lesion formation in apoE-deficient mice"J Clin Invest.. 110(3). 331-334 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ozaki M: "Overexpression of endothelial nitric oxide synthase in endothelial cells is protective against ischemia-reperfusion injury in mouse skeletal muscle"Am J Pathol.. 160(4). 1335-1344 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Azumi H: "Superoxide generation in directional coronary atherectomy specimens of patients with angina pectoris : important role of NAD(P)H oxidase"Arterioscler Thromb Vasc Biol.. 22(11). 1838-1844 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kobayashi S: "Expressional changes of the vascular antioxidant system in atherosclerotic coronary arteries"J Atheroscler Thromb.. 9(4). 184-190 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawashima S: "HMG-CoA reductase inhibitor has protective effects against stroke events in stroke-prone spontaneously hypertensive rats"Stroke. 34(1). 157-163 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamashita T, Kawashima S, Ozaki M, Namiki M, Satomi-Kobayashi S, Seno T, Matsuda Y, Inoue N, Hirata K, Akita H, Umetani K, Tanaka E, Mori H, Yokoyama M.: "Role of endogenous nitric oxide generation in the regulation of vascular tone and reactivity in small vessels as investigated in transgenic mice using synchrotron radiation microangiography"Nitric Oxide. 5(5). 494-503 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okuda M, Inoue N, Azumi H, Seno T, Sumi Y, Hirata Ki, Kawashima S, Hayashi Y, Itoh H, Yodoi J, Yokoyama M.: "Expression of glutaredoxin in human coronary arteries : its potential role in antioxidant protection against atherosclerosis"Arterioscler Thromb Vase Biol. 21(9). 1483-1487 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawashima S, Yamashita T, Ozaki M, Ohashi Y, Azumi H, Inoue N, Hirata K, Hayashi Y, Itoh H, Yokoyama M.: "Endothelial NO synthase overexpression inhibits lesion formation in mouse model of vascular remodeling"Arterioscler Thromb Vase Biol. 21(2). 201-207 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Seno T, Inoue N, Gao D, Okuda M, Sumi Y, Matsui K, Yamada S, Hirata K, Kawashima S, Tawa R, Imajoh-Ohmi S, Sakurai H, Yokoyama M.: "Involvement of NADH/NADPH oxidase in human platelet ROS production"Thromb Res. 103(5). 399-409 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Rikitake Y, Kawashima S, Takahashi T, Ueyama T, Ishido S, Inoue N, Hirata K, Yokoyama M.: "Regulation of tyrosine phosphorylation of PYK2 in vascular endothelial cells by lysophosphatidylcholine"Am J Physiol Heart Circ Physiol. 281(1). H266-H274 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Rikitake Y, Hirata K, Kawashima S, Takeuchi S, Shimokawa Y, Kojima Y, Inoue N, Yokoyama M.: "Signaling mechanism underlying COX-2 induction by lysophosphatidylcholine"Biochem Biophys Res Commun. 281(5). 1291-1297 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Rikitake Y, Kawashima S, Takeshita S, Yamashita T, Azumi H, Yasuhara M, Nishi H, Inoue N, Yokoyama M.: "Anti-oxidative properties of fluvastatin, an HMG-CoA reductase inhibitor, contribute to prevention of atherosclerosis in cholesterol-fed rabbits"Atherosclerosis. 154(1). 87-96 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Inoue N, Takeshita S, Gao D, Ishida T, Kawashima S, Akita H, Tawa R, Sakurai H, Yokoyama M.: "Lysophosphatidylcholine increases the secretion of matrix metalloproteinase 2 through the activation of NADH/NADPH oxidase in cultured aortic endothelial cells"Atherosclerosis. 155(1). 45-52 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Rikitake Y, Hirata K, Kawashima S, Ozaki M, Takahashi T, Ogawa W, Inoue N, Yokoyama M.: "Involvement of endothelial nitric oxide in sphingosine-1-phosphate-induced angiogenesis"Arterioscler Thromb Vase Biol. 22(1). 108-114 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sumi Y, Inoue N, Azumi H, Seno T, Okuda M, Hirata K, Kawashima S, Hayashi Y, Itoh H, Yokoyama M.: "Expression of tissue transglutaminase and elafin in human coronary artery : implication for plaque instability"Atherosclerosis. 160(1). 31-39 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Rikitake Y, Hirata K, Yamashita T, Iwai K, Kobayashi S, Itoh H, Ozaki M, Ejiri J, Shiomi M, Inoue N, Kawashima S, Yokoyama M.: "Expression of G2A, a receptor for lysophosphatidylcholine, by macrophages in murine, rabbit, and human atherosclerotic plaques"Arterioscler Thromb Vase Biol. 22(12). 2049-2053 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Azumi H, Inoue N, Ohashi Y, Terashima M, Mori T, Fujita H, Awano K, Kobayashi K, Maeda K, Hata K, Shinke T, Kobayashi S, Hirata K, Kawashima S, Itabe H, Hayashi Y, Imajoh-Ohmi S, Itoh H, Yokoyama M.: "Superoxide generation in directional coronary atherectomy specimens of patients with angina pectoris : important role of NAD(P)H oxidase"Arterioscler Thromb Vase Biol. 22(11). 1838-1844 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kobayashi S, Inoue N, Azumi H, Seno T, Hirata K, Kawashima S, Hayashi Y, Itoh H, Yokozaki H, Yokoyama M.: "Expressional changes of the vascular antioxidant system in atherosclerotic coronary arteries"J Atheroscler Thromb. 9(4). 184-190 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ozaki M, Kawashima S, Yamashita T, Hirase T, Namiki M, Inoue N, Hirata K, Yasui H, Sakurai H, Yoshida Y, Masada M, Yokoyama M.: "Overexpression of endothelial nitric oxide synthase accelerates atherosclerotic lesion formation in apoE-deficient mice"J Clin Invest. 110(3). 331-340 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ozaki M, Kawashima S, Hirase T, Yamashita T, Namiki M, Inoue N, Hirata K, Yokoyama M.: "Overexpression of endothelial nitric oxide synthase in endothelial cells is protective against ischemia-reperfusion injury in mouse skeletal muscle"Am J Pathol. 160(4). 1335-1344 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawashima S, Yamashita T, Miwa Y, Ozaki M, Namiki M, Hirase T, Inoue N, Hirata K, Yokoyama M.: "HMG-CoA reductase inhibitor has protective effects against stroke events in stroke-prone spontaneously hypertensive rats"Stroke terol-fed rabbits. 34(1). 157-163 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamashita T: "Images in cardiovascular medicine. Mouse coronary angiograph using synchrotron radiation microangiography"Circulation. 105・2. E3-E4 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Namiki M: "Local overexpression ot monocyte chemoattractant protein-1 at vessel wall induces infiltration of macrophages and formation of atherosclerotic lesion : synergism with hypercholesterolemia"Arterioscler Thromb Vase Biol.. 22・1. 115-120 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Rikitake Y: "Involvement of endothelial nitric oxide in sphingosine-1-phosphate-induced angiogenesis"Arterioscler Thromb Vasc Biol.. 22・1. 108-114 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sumi Y: "Expression of tissue transglutaminase and elafin in human coronary artery. Implication for plaque instability"Atheroscierosis. 160・1. 31-39 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Rikitake Y: "Expression of G2A, a receptor for lysophosphatidylcholine, by macrophages in murine, rabbit, and human atherosclerotic plaques"Arterioscier Thromb Vase Biol.. 34・1. 157-163 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kawashima M: "HMG-CoA recluctase inhibitor has protective effects against stroke events in stroke-prone spontaneously hypertensive rats"Stroke. 34・1. 157-163 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ozaki M: "Overexpression of endoihelial nitric oxide synthase in endothelial cells protective against ischemia-reperfusion injury in mouse skeletal muscle"Am J Pathol. 160・4. 1335-1344 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamashita T: "Propagermanium reduces atherosclerosis in apolipoprotein E knockout mice via inhibition of macrophage infiltration"Arterioscier Thromb Vase Biol.. 22・6. 969-974 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ozaki M: "Overexpression of enclothelial nitric oxide synthase accelerates atherosclerotic lesion formation in apoE-deficient mice"J Clin invest.. 110・3. 331-340 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ozaki M: "Overexpiession of endothelial nitric oxide synthase attenuates cardiac hypertrophy induced by chronic isoproterenol infusion"Cir J.. 66・9. 184-190 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kobayashi S: "Expressional changes of the vascular antioxidant system in atherosclerotic coronary arteries"J. Atheroscier, Thromb.. 9・4. 184-190 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamashita M: "In vivo angiographic detection of vascular lesions in apolipoprotein E-knockout mice using a synchrotron radiation microangiography system"Circ J.. 66・11. 1057-1059 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Azumi: "Superoxide generation in directional coronary athereclomy specimens of patients with angina pectoris : important role of NAD(P)H oxidase"Arterioscier Thromb Vasc Biol. 22・11. 1838-1844 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamashita T: "Role of endogenous nitric oxide generation in the regulation of vascular tone and reactivity in small vessels as investigated in transgenic mice using synchrotron radiation microangiography"Nitric Oxide. 5・5. 494-503 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Okuda M: "Expression of glutaredoxin in human coronary arteries : its potential role in antioxidant protection against atherosclerosis"Arterioscier Thromb Vasc Biol.. 21・9. 1483-1487 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamashita T: "Images in cardiovascular medicine. Mouse coronary angiograph using synchrotron radiation microangiography"Circulation. 105(2). E3-E4 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Namiki M: "Local overexpression of monocyte chemoattractant protein-1 at vessel wall induces infiltration of macrophages and formation of atherosclerotic lesion : synergism with hypercholesterolemia"Arterioscler Thromb Vasc Biol.. 22(1). 115-120 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Rikitake Y: "Involvement of endothelial nitric oxide in sphingosine-1-phosphate-induced angiogenesis"Arterioscler Thromb Vasc Biol.. 22(1). 108-114 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sumi Y: "Expression of tissue transglutaminase and elafin in human coronary artery. Implication for plaque instability"Atherosclerosis. 160(1). 31-39 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamashita T: "Role of endogenous nitric oxide generation in the regulation of vascular tone and reactivity in small vessels as investigated in transgenic mice using synchrotron radiation microangiography"Nitric Oxide. 5(5). 494-503 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Okuda M: "Expression of glutaredoxin in human coronary arteries : its potential role in antioxidant protection against atherosclerosis"Arterioscler Thromb Vasc Biol.. 21(9). 1483-1487 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-03-31   Modified: 2016-04-21  

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