2002 Fiscal Year Final Research Report Summary
Basic and clinical studies on the role of inflammatory mechanisms in the pathogenesis ischemic heart disease
| Project/Area Number |
12470158
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Kyushu University |
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Principal Investigator |
SHIMOKAWA Hiroaki Kyushu University, Dept of CV Med, Assos. Prof., 大学院・医学研究院, 助教授 (00235681)
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| Co-Investigator(Kenkyū-buntansha) |
MOHRI Masahiro Kyushu University, Dept of CV Med, Assis Prof., 医学部附属病院, 講師 (60264032)
MARUYAMA Ikuro Kagoshima Univ, Dept of Med Exam, Prof., 医学部, 教授 (20082282)
SUEISHI Katsuo Kyushu University, Dept of Pathol, Prof., 大学院・医学研究院, 教授 (70108710)
ICHIKI Toshihiro Kyushu University, Dept of CV Med, Assis Prof., 医学部附属病院, 助手 (80311843)
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| Project Period (FY) |
2000 – 2002
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| Keywords | Inflammation / Rho-kinase / Arteriosclerosis / Angiotensin II / Oxidative stress |
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| Research Abstract |
1) Rho-kinase is substantially involved in the inflammatory mechanisms of arteriosclerosis. The expression of Rho-kinase in vascular smooth muscle cells is upregulated by inflammatory stimuli, such as angiotensin II and IL-1β with an involvement of Nf-_KB.
2) Rho-kinase mediates hypoxia-induced downregulation of endothelial NO synthase (eNOS) in cultured human endothelial cells. Hydroxyfasudil, a specific Rho-kinase inhibitor, prevents the hypoxia-induced downregufayion of eNOS.
3) Long-term inhibition of Rho-kinase suppresses in-stent restenosis in porcine coronary arteries, in which multiple mechanisms are involved, including enhancement of VSMC apoptosis, suppression of MCP-1 expression and inflammatory cell recruitment, and suppression of collagen synthesis through TGF-bl inhibition.
4) Long-term inhibition of Rho-kinase suppresses angiotensin Il-induced formation of cardiovascular lesions by multiple mechanisms, including suppressions of NAD(P)H and TGF-β1 expression and of superoxide production.
5) Long-term inhibition of Rho-kinase suppresses cardiac allograft vasculopathy, in which inhibition of the expression of macrophage migration inhibitory factor (MIF) is involved.
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Research Products
(8 results)
