2003 Fiscal Year Final Research Report Summary
Molecular mechanisms of cerebral aneurysmal formation
| Project/Area Number |
13307043
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Kyoto University |
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Principal Investigator |
HASHIMOTO Nobuo Kyoto University, Graduate School of Medicine, Professor, 医学研究科, 教授 (40135570)
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| Co-Investigator(Kenkyū-buntansha) |
KUME Noriaki Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 講師 (20252455)
KITA Toru Kyoto University, Graduate School of Medicine, Professor, 医学研究科, 教授 (60161460)
NOZAKI Kazuhiko Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 助教授 (90252452)
NAGATA Kazuhiro Kyoto University, Institute for Frontier Medical Sciences, Professor, 再生医科学研究所, 教授 (50127114)
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| Project Period (FY) |
2001 – 2003
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| Keywords | cerebral aneurysmal / iNOS / endothelium / MMP / gene |
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| Research Abstract |
The pathogenesis of cerebral aneurysm has not been-fully understood. We have developed experimental cerebral aneurysmal models in rats and mice and analyzed expressed proteins and messenger RNAs during the process of cerebral aneurismal formation. We confirmed the decrease in eNOS in the endothelium and increase in iNOS in the smooth muscle during the process, and demonstrated that an inhibitor of iNOS and the disruption of iNOS gene inhibited the aneurysmal formation. We also demonstrated increased active MMP-2 and 9 during the process and the knockout of MMP-9 decreased the formation of cerebral aneurysm. We also detected by PCR the expression of specific molecules which are related to vascular remodeling. Finally we analyzed the candidate genes which had high linkage to aneurysmal formation in highly-aggregated Japanese families.
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