• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Role of Inducible NO Synthase (iNOS) on Atherosclerosis -Study of iNOS-Knock out Mice-

Research Project

Project/Area Number 11838018
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research InstitutionTokai University

Principal Investigator

NAKAZAWA Hiroe  Tokai University, School of Medicine, Professor, 医学部, 教授 (20110885)

Co-Investigator(Kenkyū-buntansha) ICHIMORI Kouji  Tokai Univ., School of Medicine, Assistant Professor, 医学部, 講師 (60184636)
ISHIDA Hideyuki  Tokai Univ., School of Medicine, Assistant Professor, 医学部, 講師 (20222424)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥2,600,000 (Direct Cost: ¥2,600,000)
KeywordsNO synthase / nNOS / iNOS / eNOS / knock out / LDL oxidation / macrophage
Research Abstract

Chronic inhibition of nitric oxide (NO) production accelerates atherosclerosis, while enhanced production of NO suppresses the development of atherosclerosis or even regresses the lesions. These effects of NO largely depend on its antioxidant action. On the other hand, a high flux of NO from iNOS may favor formation of peroxynitrite and produce nitrotyrosine and functions as proatherogenic. Thus, the role of inducible NOS (iNOS) in the development of atherosclerosis remains to be established. We examined the susceptibility of iNOS^<-/-> and iNOS^<+/+> mice to the development of atherosclerosis induced by an atherogenic diet and analyzed the composition of the atherosclerotic lesions in the two strains to clarify the influence of iNOS on the atherogenesis.
Plasma lipid level, atherosclerotic lesion size and cellular density in the lesions were all similar in the two strains (lesion size : iNOS^<+/+> 285±73 vs. iNOS^<-/-> 293±82×10^3 μm^2, n=10). iNOS mRNA was detected in the lesions of iNOS^<+/+> but not iNOS^<-/-> mice by a reverse transcriptase-polymerase chain reaction (RT-PCR) method. Immunohistochemically, iNOS^<+/+> mice showed iNOS staining in macrophages and medial smooth muscle cells in the lesions. Nitrotyrosine staining showed a similar distribution, whereas it was absent in iNOS^<-/-> mice. There was no apparent difference in the intensity or distribution of VCAM-1 staining in the lesions of the two strains. However, the lesions of iNOS^<+/+> mice showed a markedly decreased extracellular collagen content compared with those of iNOS^<-/-> mice
iNOS induction does not affect the development of atherosclerosis in mice fed an atherogenic diet, but the resulting lesions show decreased levels of extracellular collagen, and may be more fragile.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (43 results)

All Other

All Publications (43 results)

  • [Publications] Xi-Lin Niu: "Inducible nitric oxide synthase deficiency does not affect susceptibility of mice to atherosclerosis but increases collagen content in lesions."Circulation. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Asahi K: "Nitric oxide inhibits the formation of advanced glycation end products."Kidney Int. 58. 1780-1787 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hirabayashi H: "Nitrotyrosine generation via inducible nitric oxide synthase in vascular wall in focal ischemia-reperfusion."Brain Res. 852. 319-325 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Niu Xi Lin: "Tanshinone II-A inhibits low density lipoprotein oxidation in viro."Free Rad Res. 33. 305-312 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hayashi Y: "P-selectin participates in cardiopulmonary bypass-induced inflammatory response in association with nitric oxide and peroxynitrite production."J Thorac Cardiovasc Surg. 120. 558-565 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Niu Xi-Lin: "Inducible Nitric Oxide Synthase knockout Mouse Macrophages Disclose Prooxidant Effect of Interferon-γ on Low-Density Lipoprotein Oxidation."Nitric Oxide : Biol and Chem. 4. 363-371 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tsuji C: "Nakazawa H : Increased production of nitrotyrosine in lung tissue of rats with radiation-induced acute lung injury."Am J Physiol Lung Cell Mol Physiol. 278. L719-L725 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hayashi Y: "MET-88, a γ-butyrobetain hydroxylase inhibitor improves cardiac SR Ca2+ uptake activity in rats with congestive heart failure following myocardial infarction."Mol Cell Biochem. 209. 39-46 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kato T: "Calmodulin kinases II and IV and calcineurin are involved in leukemia inhibitory factor-induced cardiac hypertrophy in rats."Circ Res. 87. 937-945 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takizawa S: "Dynamics of nitrotyrosine formation and decay in rat brain during focal ischemia."J Cereb Blood F Met. 19. 667-672 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Xiao-Shu Cheng: "Role of superoxide anion in the pathogenesis of cytokine-induced myocardial dysfunction in dogs in vivo."Cardiovasc Res. 42. 651-659 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hirabayshi H: "7-Nitroindazole attenuates nitrotyrosine formation in the early phase of cerebral ischemia-reperfusion in mice."Neuroscience Letters. 268. 111-113 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hasegawa S: "Apoptosis of hepatocytes is a main cause of inducing lethal hepatic failure after excessive hepatectomy in rats."Transplant Proc. 31. 558-559 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ichimori K: "Synthesis and evaluation of new sulfur-containing L-arginine-derived inhibitors of nitric oxide synthase."J Med Chem. 20. 1842-1848 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Honda K: "Inhaled nitric oxide reduces tyrosine after LPS instillation in Lung Tissue of Rats."Am J Respir Crit Care Med. 160. 678-688 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ishida H: "District roles of peroxynitrite and hydroxyl radical in triggering stunned myocardium-like impairment of cardiac myocytes in vitro."Mol Cell Biochem. 198. 31-38 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Xi-Lin Niu: "Inducible nitric oxide synthase deficiency does not affect susceptibility of mice to atherosclerosis but increases collagen content in lesions."Circulation. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Asahi K: "Nitric oxide inhibits the formation of advanced glycation end products."Kidney Int. 58. 1780-1787 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hirabayashi H: "Nitrotyrosine generation via inducible nitric oxide synthase in vascular wall in focal ischemia-reperfusion."Brain Res. 852. 319-325 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Niu Xi-Lin: "Tanshinone II-A inhibits low density lipoprotein oxidation in viro."Free Rad Res. 33. 305-312 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hayashi Y: "P-selectin participates in cardiopulmonary bypass-induced inflammatory response in association with nitric oxide and peroxynitrite production."J Thorac Cardiovasc Surg. 120. 558-565 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Niu Xi-Lin: "Inducible Nitric Oxide Synthase knockout Mouse Macrophages Disclose Prooxidant Effect of Interferon-γ on Low-Density Lipoprotein Oxidation."Nitric Oxide : Biol and Chem. 4. 363-371 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tsuji C: "Increased production of nitrotyrosine in lung tissue of rats with radiation-induced acute lung injury."Am J Physiol Lung Cell Mol Physiol. 278. L719-L725 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hayashi Y: "MET-88, a γ-butyrobetain hydroxylase inhibitor, comproves cardiac SR Ca2+ uptake activity in rats with congestive heart failure following myocardial infarction."Mol Cell Biochem. 209. 39-46 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kato T: "Calmodulin kinases II and IV and calcineurin are involved in leukemia inhibitory factor-induced cardiac hypertrophy in rats."Circ Res. 87. 937-45 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hirabayshi H: "7-Nitroindazole attenuates nitrotyrosine formation in the early phase of cerebral ischemia-reperfusion in mice."Neuroscience Letters. 268. 111-113 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Xiao-Shu Cheng: "Role of superoxide anion in the pathogenesis of cytokine-induced myocardial dysfunction in dogs in vivo."Cardiovasc Res. 42. 651-659 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takizawa S: "Dynamics of nitrotyrosine formation and decay in rat brain during focal ischemia."J Cereb Blood F Met. 19. 667-672 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hasegawa S: "Apoptosis of hepatocytes is a main cause of inducing lethal hepatic failure after excessive hepatectomy in rats."Transplant Proc. 31. 558-9 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ichimori K: "Synthesis and evaluation of new sulfur-containing L-arginine-derived inhibitors of nitric oxide synthase."J Med Chem. 20. 1842-8 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Honda K: "Inhaled nitric oxide reduces tyrosine after LPS instillation in Lung Tissue of Rats."Am J Respir Crit Care Med. 160. 678-688 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ishida H: "District roles of peroxynitrite and hydroxyl radical in triggering stunned myocardium-like impairment of cardiac myocytes in vitro."Mol Cell Biochem. 198. 31-38 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Xi-Lin Niu: "Inducible nitric oxide synthase deficiency does not affect susceptibility of mice to atherosclerosis but increases collagen content in lesions."Circulation. (in press). (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Asahi K: "Nitric oxide inhibits the formation of advanced glycation end products."Kidney Int. 58. 1780-1787 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hirabayashi H: "Nitrotyrosine generation via inducible nitric oxide synthase in vascular wall in focal ischemia-reperfusion."Brain Res. 852. 319-325 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Niu Xi Lin: "Tanshinone II-A inhibits low density lipoprotein oxidation in viro."Free Rad Res. 33. 305-312 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hayashi Y: "P-selectin participates in cardiopulmonary bypass-induced inflammatory response in association with nitric oxide and peroxynitrite production."J Thorac Cardiovasc Surg. 120. 558-565 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Niu Xi-Lin: "Inducible Nitric Oxide Synthase knockout Mouse Macrophages Disclose Prooxidant Effect of Interferon-γ on Low-Density Lipoprotein Oxidation."Nitric Oxide : Biol and Chem. 4. 363-371 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tsuji C: "Nakazawa H : Increased production of nitrotyrosine in lung tissue of rats with radiation-induced acute lung injury."Am J Physiol Lung Cell Mol Physiol. 278. L719-L725 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hayashi Y: "MET-88, aγ-butyrobetain hydroxylase inhibitor improves cardiac SR Ca2+ uptake activity in rats with congestive heart failure following myocardial infarction."Mol Cell Biochem. 209. 39-46 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kato T: "Calmodulin kinases II and IV and calcineurin are involved in leukemia inhibitory factor-induced cardiac hypertrophy in rats."Circ Res. 87. 937-945 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Genka C: "Visualization biphasic Ca2+ diffusion from cytosol to nucleus in contracting adult rat cardiac myocytes with an ultra-fast confocal imaging system"Cell Calcium. 25. 199-208 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Murata M: "Leukemia inhibitory factor, a potent cardiac hypertrophic cytokine, enhances L-type Ca^<2+> current and [Ca^<2+>] i transient in cardiomyocytes"J Mol Cell Cardiol. 31. 237-245 (1999)

    • Related Report
      1999 Annual Research Report

URL: 

Published: 1999-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi