1999 Fiscal Year Final Research Report Summary
Experimental and Clinical Studies on the Role of Inflammatory Mechanisms in the Pathogenesis of Ischemic Heart Disease
| Project/Area Number |
09470169
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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 Horoaki Kyushu Univ. Graduate Sch., Dept. of Cardiovasc Med., Asso. Pro., 大学院・医学系研究科, 助教授 (00235681)
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| Co-Investigator(Kenkyū-buntansha) |
MOHRI Masahiro Kyushu Univ. Sch. of Med., Dept. of Cardiovasc Med., Assist. Pro., 医学部, 助手 (60264032)
MARUYAMA Ikuro Kagoshima Univ. Dept. of Laboratory Med., Prof., 医学部, 教授 (20082282)
SUEISHI Katuso Kyushu Univ. Graduate Sch., Dept. of Pathology, Asso. Pro., 大学院・医学系研究科, 教授 (70108710)
SATOH Shinji Kyushu Univ. Graduate Sch., Dept. of Cardiovasc Med., Adjunct Assist. Prof., 大学院・医学系研究科, 助手 (60274445)
OHARA Yuichi Kyushu Univ. Sch. of Med., Dept. of Cardiovasc Med., Adjunct Assist. Prof., 医学部, 助手 (90185364)
ICHKI Toshihiro Kyushu Univ. Sch. of Med., Dept. of Cardiovasc Med., Asso. Adjunct Assist. Prof. (80311843)
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| Project Period (FY) |
1997 – 1999
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| Keywords | cytokines / atherosclerosis. / coronary artery spasm / vascular remodeling / nitric oxide / small G proteins / Rho-kinase / gene therapy |
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| Research Abstract |
(Experimental studies)
1. The long-term adventitial treatment with IL-1βresulted in the development of vascular remodeling and neointimal formation of the porcine coronary artery in vivo, whereas endothelial vasodilator functions were fairly preserved.
2. In this porcine model, inducible NO synthase (iNOS) was transiently expressed in VSMC and exerted an inhibitory effect against vascular lesion formation in vivo.
3. Regarding the molecular mechanism of the coronary artery spasm in this porcine model, it was shown that Rho-kinase is upregulated and inhibits myosin phosphatase, resulting in the increased myosin phosphorylations and hypercontractions of VSMC.
4. We have established the method of in vivo gene transfer into the coronary artery in vivo using the infiltrator balloon angioplasty catheter (IABC). Using this novel method, we were able to inhibit the neointimal formation after balloon injury in porcine coronary arteries by overexpressing CNP in vivo.
5. The long-term inhibitation of Rho-kinase by either hydroxyfasudil (a specific inhibitor of Rho-kinase) or in vivo gene transfer of dominant negative Rho-kinase resulted in the regression of vascular remodeling caused by inflammatory cytokines.
(Clinical studies)
In patients with coronary artery disease, the plasma levels of macrophage-colony stimulating factor (M-CSF) were increased while those of transforming factor-b (TGF-b) were decreased, thus stimulating the process of atherosclerosis.
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