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
| Project/Area Number |
15590722
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
ISHIZAKA Nobukazu The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (20270879)
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| 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)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Angiotensin II / Oxdative Stress / Aging |
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| 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.
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