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2004 Fiscal Year Final Research Report Summary

ROLE OF ABERRANT IRON HOMEOSTASIS AND INCREASED PRODUCTION OF REACTIVE OXYGEN SPECIES IN THE DEVELOPMENT OF CARDIOVASCULAR DAMAGE INDUCED BY ANGIOTENSIN II

Research Project

Project/Area Number 15590722
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionThe University of Tokyo

Principal Investigator

ISHIZAKA Nobukazu  The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (20270879)

Co-Investigator(Kenkyū-buntansha) MORI Ichiro  Wakayama Medical University, Associate Professor, 附属病院, 助教授 (10157852)
TSUKAMOTO Kazuhisa  The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (20251233)
SATA Masataka  The University of Tokyo, Faculty of Medicine, Visiting Assistant Professor, 医学部附属病院, 寄附講座教員 (80345214)
Project Period (FY) 2003 – 2004
KeywordsAngiotensin II / Oxdative Stress / Aging
Research Abstract

We have previously reported that long-term administration of angiotensin II (Ang II) caused iron deposition in the renal tubular cells, which may have a role in the modulation of functional impairment and regulation of expression of certain genes induced by Ang II.
We have investigated whether Ang II also causes aberrant iron homeostasis in the rat cardiovascular system, and their possible relation to regulatory effects on gene expression and functions in Ang II-infused animals.
We obtained the following results.
I.Ang II, iron, and the heart
(1)Ang II infusion induced induction of ferritin expression and deposition of iron in the heart, which may exacerbate Ang II-induced cardiac fibrosis.
(2)Iron chelation attenuates these phenomena induced by Ang II without affecting hemodynamic parameters.
(3)Ang II infusion was found to increase TGF-β1 mRNA expression in the coronary artery wall, macrophages, and myofibroblast-like cells.
(4)Iron chelation also suppresses Ang II-induced upregulation of TGF-β1 mRNA.
II.Ang II, iron, and the aorta
(5)Infusion of Ang II, but not norepinephrine, induced induction of ferritin expression and deposition of iron in the rat aortas.
(6)Iron chelation upregulation of MCP-1 expression, impairment of endothelial-dependent vascular relaxation, and accumulation of peroxidized lipids
These findings collectively suggest that altered iron homeostasis. may have a role in the Ang II-induced functional damage and gene regulation in the cardiovascular tissues, presumably via enhancing the extent of oxidative stress.

  • Research Products

    (28 results)

All 2005 2004 2003 Other

All Journal Article (28 results)

  • [Journal Article] A Case of Retroperitoneal Fibrosis with Periaortic and Pericardial Involvement.2005

    • Author(s)
      Eisuke Amiya, Nobukazu Ishizaka, Airi Watanabe, Yoko Endo, Rei Itou, Shigetaka Yoshida, Masahumi Nangaku, Ryozo Nagai
    • Journal Title

      Circulation Journal (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Association between cigarette smoking, metabolic syndrome, and carotid arteriosclerosis in Japanese individuals.2005

    • Author(s)
      Nobukazu Ishizaka, Yuko Ishizaka, Ei-Ichi Toda, Hideki Hashimoto, Ryozo Nagai, Minoru Yamakado
    • Journal Title

      Atherosclerosis (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Association between Serum Uric Acid, Metabolic Syndrome, and Carotid Atherosclerosis in Japanese Individuals.2005

    • Author(s)
      Nobukazu Ishizaka, Yuko Ishizaka, Ei-Ichi Toda, Ryozo Nagai, Minoru Yamakado
    • Journal Title

      Arterioscler Thromb Vasc Biol (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Association between white blood cell count and carotid arteriosclerosis in Japanese smokers.2004

    • Author(s)
      Nobukazu Ishizaka
    • Journal Title

      Atherosclerosis 175

      Pages: 95-100

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Statins augment collateral growth in response to ischemia but they do not promote cancer and atherosclerosis.2004

    • Author(s)
      Masataka Sata
    • Journal Title

      Hypertension 43・6

      Pages: 1214-1220

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Role of Aberrant Iron Homeostasis in the Upregulation of Transforming Growth Factor-β1 in the Kidney of Angiotensin II-Induced Hypertensive Rats.2004

    • Author(s)
      Kan Saito
    • Journal Title

      Hypertension Research 27・8

      Pages: 599-607

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Iron dextran causes renal iron deposition but noto renal dysfunctior in angiotensin II-treated and untreated rats.2004

    • Author(s)
      Nobukazu Ishizaka
    • Journal Title

      Nephron Physiology 98・4

      Pages: 107-113

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Association between white blood cell count and carotid arteriosclerosis in Japanese smokers.2004

    • Author(s)
      Nobukazu Ishizaka, Yuko Ishizaka, Ei-ichi Toda, Hideki Hashimoto, Ryozo Nagai, Minoru Yamakado.
    • Journal Title

      Atherosclerosis 175

      Pages: 95-100

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Statins augment collateral growth in response to ischemia but they do not promote cancer and atherosclerosis.2004

    • Author(s)
      Masataka Sata, Hiroaki Nishimatsu, Jun-ichi Osuga, Kimie Tanaka, Nobukazu Ishizaka, Shun Ishibashi, Yasunobu Hirata, Ryozo Nagai.
    • Journal Title

      Hypertension. 43(6)

      Pages: 1214-1220

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Role of Aberrant Iron Homeostasis in the Upregulation of Transforming Growth Factor-β1 in the Kidney of Angiotensin II-Induced Hypertensive Rats.2004

    • Author(s)
      Kan Saito, Nobukazu Ishizaka, Toru Aizawa, Masataka Sata, Naoyuki Iso-o, Eisei Norii, Minoru Ohno, Ryozo Nagai
    • Journal Title

      Hypertension Research 27(8)

      Pages: 599-607

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Iron dextran causes renal iron deposition but not renal dysfunction in angiotensin II-treated and untreated rats.2004

    • Author(s)
      Nobukazu Ishizaka, Kan Saito, Eisei Noiri, Masataka Sata, Ichiro Mori, Minoru Ohno, Ryozo Nagai.
    • Journal Title

      Nephron Physiology 98(4)

      Pages: 107-113

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Administration of angiotensin II induces iron deposition and upregulation of TGF-β1 mRNA in the rat liver.2004

    • Author(s)
      Nobukazu Ishizaka, Kan Saito, Eisei Noiri, Masataka Sata, Hitoshi Ikeda, Akihiko Ohno, Jiro Ando, Ichiro Mori, Minoru Ohno, Ryozo Nagai
    • Journal Title

      Am J Physiol Regul Integr Comp Physiol (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Hypertension is the Most Common Component of Metabolic Syndrome and the Greatest Contributor to Carotid Arteriosclerosis in Apparently Healthy Japanese Individuals.2004

    • Author(s)
      Nobukazu Ishizaka, Yuko Ishizaka, Ei-Ichi Toda, Hideki Hashimoto, Ryozo Nagai, Minoru Yamakado
    • Journal Title

      Hypertension Research (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Iron chelation and a free radical scavenger suppress angiotensin II-induced upregulation of TGF-β1 in the heart.2004

    • Author(s)
      Kan Saito, Nobukazu Ishizaka, Toru Aizawa, Masataka Sata, Naoyuki Iso-o, Eisei Noiri, Ichiro Mori, Minoru Ohno, Ryozo Nagai
    • Journal Title

      Am J Physiol Heart Circ Physiol (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Facilitated angiogenesis induced by heme oxygenase-1 gene transfer in a rat model of hindlimb ischemia.2003

    • Author(s)
      Masatoshi Suzuki
    • Journal Title

      Biochem Biosophys Res Commun 302・1

      Pages: 134-143

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Induction of renoprotective gene expression by cobalt ameliorates ischemic injury of the kidney in rats.2003

    • Author(s)
      Makiko Matsumoto
    • Journal Title

      J Am Soc Nephrol 14・7

      Pages: 1825-1832

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Absence of p53 leads to accelerated neointimal hyperplasia after vasucular injury.2003

    • Author(s)
      Masataka Sata
    • Journal Title

      Arterioscler Thromb Vasc Biol 23・9

      Pages: 1548-1552

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Iron chelation and a free radical scavenger suppress Angiotensin II-induced downregulation of klotho, an anti-aging gene in rat.2003

    • Author(s)
      Kan Saito
    • Journal Title

      FEES Letters 551・1-3

      Pages: 58-62

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Facilitated angiogenesis induced by heme oxygenase-1 gene transfer in a rat model of hindlimb ischemia.2003

    • Author(s)
      Masatoshi Suzuki, Naoyuki Iso-o, Satoshi Takeshita, Kazuhisa Tsukamoto, Ichiro Mori, Tomohide Sato, Minoru Ohno, Ryozo Nagai, Nobukazu Ishizaka.
    • Journal Title

      Biochem Biophys Res Commun 302(1)

      Pages: 138-143

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Induction of renoprotective gene expression by cobalt ameliorates ischemic injury of the kidney in rats.2003

    • Author(s)
      Makiko Matsumoto, Yuichi Makino, Tetsuro Tanaka, Hiroshi Tanaka, Nobukazu Ishizaka, Eisei Noiri, Toshiro Fujita, Masaomi Nangaku.
    • Journal Title

      J Am Soc Nephrol 14(7)

      Pages: 1825-1832

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Absence of p53 leads to accelerated neointimal hyperplasia after vascular injury.2003

    • Author(s)
      Masataka Sata, Kimie Tanaka, Nobukazu Ishizaka, Yasunobu Hirata, Ryozo Nagai.
    • Journal Title

      Arterioscler Thromb Vasc Biol 23(9)

      Pages: 1548-1552

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Iron chelation and a free radical scavenger suppress Angiotensin II-induced downregulation of klotho, an anti-aging gene in rat.2003

    • Author(s)
      Kan Saito, Nobukazu Ishizaka, Haruo Mitani, Minoru Ohno, Ryozo Nagai.
    • Journal Title

      FEBS Letters 551(1-3)

      Pages: 58-62

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Administration of angiotensin II induces iron deposition and upregulation of TGF β-1 mRNA in the rat liver.

    • Author(s)
      Nobukazu Ishizaka
    • Journal Title

      Am J Physiol Regul Integr Comp Physiol (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Hypertension is the Most Common Component of Metabolic Syndrome and the Greatest Contributor to Carotid Arteriosclerosis in Apparently Healthy Japanese Individuals.

    • Author(s)
      Nobukazu Tshizaka
    • Journal Title

      Hypertension Research (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Iron chelation and a free radical scavenger suppress angiotensin II-induced upregulation of TGF-β1 in the heart.

    • Author(s)
      Kan Saito
    • Journal Title

      Am J Physiol Heart Circ Physiol (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A Case of Retroperitoneal Fibrosis with Periaortic and Pericardial Involvement.

    • Author(s)
      Eisuke Amiya
    • Journal Title

      Circulation Journal (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Association between cigarette smoking, metabolic syndrome, and carotid arteriosclerosis in Japanese individuals.

    • Author(s)
      Nobukazu Ishizaka
    • Journal Title

      Atherosclerosis (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Association between Serum Uric Acid, Metabolic Syndrome, and Carotid Atherosclerosis in Japanese Individuals.

    • Author(s)
      Nobukazu Ishizaka
    • Journal Title

      Arterioscler Thromb Vasc Biol (印刷中)

    • Description
      「研究成果報告書概要(和文)」より

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Published: 2006-07-11  

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