| Project/Area Number |
09835006
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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 |
老化(加齢)
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| Research Institution | Osaka University |
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Principal Investigator |
FUKUO Keisuke Osaka University Medical School, Lecturer, 医学部, 講師 (40156758)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAHASHI Takeshi Osaka University Medical School, Medical Staff, 医学部・附属病院, 医員
HIROTANI Atsushi Osaka University Medical School, Medical Staff, 医学部・附属病院, 医員
MORIMOTO Shigeto Osaka University Medical School, Associate Professor, 医学部, 助教授 (20150336)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Nitric Oxide / Apoptosis / Fas / Plaque Rupture / Vascular Smooth Muscle / Oxidant Stress |
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| Research Abstract |
Recent evidence has shown that rupture of vulnerable plaque with thrombosis is a critical trigger for the development of cardiovascular events.Within selected, cellular regions of many of the atherosclerotic lesions, marked apoptosis is present in vascular cells and that this can occur virtually in the absence of cellular proliferation.However, it is not clear how apoptotic process participate in the genesis of plaque rupture in the atherosclerotic lesions.In this project we first focused on the regulatory mechanism of apoptosis in the vascular cells using a cell culture system.We found that oxidative stress H2O2 induces up-regulation of Fas in endothelial cells (ECs) and that activation of protein tyrosine kinase may be involved in the mechanism of H2O2-induced Fas expression.Although cellular defense mechanisms against the cytotoxic actions of nitric oxide (NO) in the arterial wall are not clear, we also found that vascular endothelial growth factor (VEGF) released from vascular smooth muscle cells (VSMCs) protect ECs from NO-induced apoptosis at down-stream of p53-mediated pathway.Thus, ECs in the VSMC-poor plaques may be more susceptible to NO-induced cytotoxicity.We are now trying to investigate these possibilities using animal models.
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