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Role of Vascular NADH/NAPDH oxidase in atherogenesis

Research Project

Project/Area Number 12470154
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

YOKOYAMA Mitsuhiro  Kobe University, Graduate School of Medicine, Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Professor, 医学部・附属病院, 教授 (40135794)

Co-Investigator(Kenkyū-buntansha) 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)
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) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2001: ¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 2000: ¥8,800,000 (Direct Cost: ¥8,800,000)
Keywordssuperoxide / atherosclerosis / glutathione peroxidase / NADH / NADPH oxidase / coronary artery disease / oxidized LDL / 冠動脈 / 免疫染色法 / NO合成酵素 / NADH oxidase
Research Abstract

Oxidative stress induced by reactive oxygen species (ROS) is implicated in the pathogenesis of a variety of vascular diseases including atherosclerosis and coronary artery disease. NADH/NADPH oxidase is an important source of reactive oxygen species (ROS).
Recently, we demonstrated that p22^<phox>, an essential component of this oxidase, was expressed in human coronary arteries, and its expression was enhanced with the progression of atherosclerosis. The present study was undertaken to investigate the functional importance of NADH/NADPH oxidase in pathogenesis of various vascular diseases.
We examined the effect of lysophosphatidylcholine (LPC), atherogenic component of oxidized LDL, on the activity of NADH/NADPH oxidase in cultured endthelial cells. Homogenates of cultured aortic endothelial cell had the enzymatic activity of NADH/NADPH. LPC induced O_2-generation. Thus the production of O_2-in endothelial cells is mainly mediated by the NADH/NADPH oxidase system and LPC activates this oxidase to enhance O_2-production.
The functional role of NADH/NADPH oxidase in pathpgenesis of atherosclerotic corbriary disease was investigated. For this aim, the expression of p22^<phox>, distribution of oxidized LDL and generation of ROS in directional coronary atherectomy (DCA) specimens were examined. DCA specimens were obtained from patients with stable (SAP) or unstable angina pectoris (UAP). ROS generation was closely associated, with the distribution of p22^<phox> and oxidized LDL. There was a correlation between ROS and the expression of p22^<phox> or oxidized LDL. These factors of UAP were significantly higher compared with SAP. ROS generated by p22^<pfox> -based NADH/NADPH oxidase likely mediate oxidative modification of LDL, and it might play a major role in pathogenesis of atherosclerotic coronary artery disease.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report

Research Products

(59 results)

All Other

All Publications (59 results)

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

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [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"Arterioscier Thromb Vase Biol.. 22(1). 115-120 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Rikitake Y: "Involvement of endothelial nitric oxide in sphingosine-1-phosphate-induced angiogenesis"Arterioscier Thromb Vasc Biol.. 22(1). 108-114 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 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
      2001 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 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
      2001 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). 281(1)H266-281(1)H274 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamashita T: "A calcium channel blocker, benidipine, inhibits intimal thickening in the carotid artery of mice by increasing nitric oxide production"J Hypertens.. 19(3). 451-458 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 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
      2001 Final Research Report Summary
  • [Publications] Ishida T: "Serotonin-induced hypercontraction through 5-hydroxytryptamine 1B receptors in atherosclerotic rabbit coronary arteries"Circulation. 103(9). 1289-1295 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ozaki M: "Reduced hypoxic pulmonary vascular remodeling by nitric oxide from the endothelium"Hypertension. 37(2). 322-327 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 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. 55(1). 45-52 (2001)

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

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 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"Atherosclerosis. 154(1). 87-96 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takeshita S: "Lysophosphatidylcholine enhances superoxide anions production via endothelial NADH/NADPH oxidase"J Atheroscier Thromb. 7(4). 238-246 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Rikitake Y: "Inhibition of endothelium-dependent arterial relaxation by oxidized phosphatidylcholine"Atherosclerosis. 152(1). 79-87 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamashita T: "Mechanisms of reduced nitric oxide/cGMP-mediated vasorelaxation in transgenic mice overexpressing endothelial nitric oxide synthase"Hypertension. 36(1). 97-102 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takeshita S: "Shear stress enhances glutathione peroxidase expression in endothelial cells"Biochem Biophys Res Commun.. 273(1). 66-71 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takeshita S: "Mechanical stress modulates glutathione peroxidase expression in cultured bovine aortic endothelial cells"Ann N Y Acad Sci.. 902. 298-301 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yokoyama M: "Role of the vascular NADH/NADPH oxidase system in atherosclerosis"Ann N Y Acad Sci.. 902. 241-247 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamashita T: "Resistance to endotoxin shock in transgenic mice overexpressing endothelial nitric oxide synthase"Circulation. 101(8). 931-937 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takeuchi S: "Cerivastatin suppresses lipopolysaccharide-induced ICAM-1 expression through inhibition of Rho GTPase in BAEC"Biochem Biophys Res Commun.. 269(1). 97-102 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamashita T, Kawashima S, Ozaki M, Namiki M, Hirase T, Inoue N, Hirata K, Umetani K, Sugimura K, Yokoyama M.: "ages in cardiovascular medicine. Mouse coronary angiograph using synchrotron radiation microangiography"Circulation. 105(2). E3-4 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Namiki M, Kawashima S, Yamashita T, Ozaki M, Hirase T, Ishida T, Inoue N, Hirata K, Matsukawa A, Morishita R, Kaneda Y, Yokoyama 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 Vase Biol.. 22(1). 115-20 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 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). 108-14 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 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). 31-9 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 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 Oxidey. 5(5). 494-503 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 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 pptential role in antioxidant protection against atherosclerosis"Arterioscler Thromb Vase Biol.. 21(9). 1483-7 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Seno T, Inoue N, Gao D, Okuda M, Sumi Y, Matsui K, Yamada S, Hirata KI, 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
      2001 Final Research Report Summary
  • [Publications] Takeshita S, Inoiie N, Gao D, Rikitake Y, Kawashima S, Tawa R, Sakurai H, Yokoyama M.: "Lysophdsphatidylcholine enhances superoxide anions production via endothelial NADH/NADPH oxidase"J Atheroscler Thromb.. 7(4). 238-46 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 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). H266-74 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamashita T, Kawashima S, Ozaki M, Rikitake Y, Hirase T, Inoue N, Hirata K, Yokoyama M.:

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] "A calcium channel blocker, benidipine, inhibits intimal thickening in the carotid artery of mice by increasing nitric oxide production."J Hypertens.. 19(3). 451-8 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 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). 1291-7 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ishida T, Kawashima S, Hirata KI, Sakoda T, Shimokawa Y, Miwa Y, Inoue N, Ueyama t, Shiomi M, Akita H, Yokoyama M.: "Serotonin-induced hypercontraction through 5-hydroxytryptamine 1B receptors in atherosclerotic rabbit coronary arteries"Circulation. 103(9). 1289-95 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ozaki M, Kawashima S, Yamashita T, Ohashi Y, Rikitake Y, Inoue N, Hirata KI, Hayashi Y, Itoh H, Yokoyama M.: "Reduced hypoxic pulmonary vascular remodeling by nitric oxide from the endothelium"Hypertension. 37(2). 322-7 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Inoue N, Takeshita S, Gao D, Ishida T, Kawashima S, Akita H, Tawa R, Sakurai H, Yokoyama M.: "Lysophospnatidylcholme 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
      2001 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 Vasc Biol. 21(2). 201-7 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 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
      2001 Final Research Report Summary
  • [Publications] Rikitake Y, Hirata K, Kawashima S, Inoue N, Akita H, Kawai Y, Nakagawa Y, Yokoyama M: "Inhibition of endothelium-dependent arterial relaxation by oxidized phosphatidylcholine"Atherosclerosis. 152(1). 79-87 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamashita T, Kawashima S, Ohashi Y, Ozaki M, Rikitake Y, Inoue N, Hirata K, Akita H, Yokoyama M.: "Mechanisms of reduced nitric oxide/cGMP-mediated vasorelaxation in transgenic mice overexpressing endothelial nitric oxide synthase"Hypertension. 36(1). 97-102 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takeshita S, Inoue N, Ueyama T, Kawashima S, Yokoyama M: "Shear stress enhances glutathione peroxidase expression in endothelial cells"Biochem Biophys Res Commun. 273(1). 66-71 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takeshita S, Inoue N, Rikitake Y, Kawashima S, Yokoyama M: "Mechanical stress modulates glutathione peroxidase expression in cultured bovine aortic endothelial cells"Ann N Y Acad Sci. 902. 298-301 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yokoyama M, Inoue N, Kawashima S.: "Role of the vascular NADH/NADPH oxidase system in atherosclerosis"Ann N Y Acad Sci.. 902. 241-7; discussion 247-8 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamashita T, Kawashima S, Ohashi Y, Ozaki M, Ueyama T, Ishida T, Inoue N, Hirata K Akita H, Yokoyama M: "Resistance to endotoxin shock in transgenic mice overexpressing endothelial nitric oxide synthase"Circulation. 101(8). 931-7 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takeuchi S, Kawashiitia S, Rikitake Y, Ueyama T, Inoue N, Hirata K, Yokoyama M.: "Cerivastatin suppresses lipopolysaccharide-induced ICAM-1 expression through inhibition of Rho GTPase in BAEC"Biochem Biophys Res Commun. 269(1). 97-102 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamashita T: "Images in cardiovascular medicine. Mouse coronary angiograph using sychrotron 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 or endogenous nitric oxide generation in the regulation of vascular tone and reactivity in small vessels as investigated in transgenic mine 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
  • [Publications] Saori Takeshita: "Shear stress enhances glutathione peroxidase expression in endothelial cells."Biochem Biophys Res Commun.. 273. 66-71 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tomoya Yamashita: "Mechanisms of reduced nitric oxide/cGMP-mediated vasorelaxation in transgenic mice overexpressing endothelial nitric oxide synthase."Hypertension.. 36. 97-102 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yoshiyuki Rikitake: "Inhibition of endothelium-dependent arterial relaxation by oxidized phosphatidylcholine."Atherosclerosis.. 152. 79-87 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yoshiyuki Rikitake: "Anti-oxidative properties of fluvastatin, an HMG-CoA reductase inhibitor, contribute to Prevention of atherosclerosis in cholesterol-fed rabbits"Atherosclerosis.. 154. 87-96 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Seinosuke Kawashima: "Endothelial NO Synthase Overexpression Inhibits Lesion Formation in Mouse Model of Vascular Remodeling."Arterioscler Thromb Vasc Biol.. 21. 201-207 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nobutaka Inoue: "Lysophosphatidylcholine increases the secretion of matrix metalloproteinase 2 through the activation of NADH/NADPH oxidase in cultured aortic endothelial cells."Atherosclerosis.. 155. 45-52 (2001)

    • Related Report
      2000 Annual Research Report

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Published: 2000-03-31   Modified: 2016-04-21  

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