2004 Fiscal Year Final Research Report Summary
STRESS-ACTIVATED SIGNALING PATHWAY AND GENE ANALYSIS IN VASCULAR CELLS DERIVED FROM PATIENTS WITH MOYAMOYA DISEASE
| Project/Area Number |
15591510
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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 |
Cerebral neurosurgery
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| Research Institution | TOKYO MEDICAL & DENTAL UNIVERSITY |
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Principal Investigator |
AOYAGI Masaru TOKYO MEDICAL & DENTAL UNIVERSITY, GRADUATE SCHOOL, ASSOCIATE PROFESSOR, 大学院・医歯学総合研究科, 助教授 (40134704)
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| Co-Investigator(Kenkyū-buntansha) |
WAKIMOTO Hiroaki TOKYO MEDICAL & DENTAL UNIVERSITY, INSTRUCTOR, 大学院・医歯学総合研究科, 助手 (30270507)
TORIYAMA Hideuki TOKYO MEDICAL & DENTAL UNIVERSITY, INSTRUCTOR, 医学部・附属病院, 助手 (20334435)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Moyamoya disease / Vascular smooth muscle cells / COX-2 / MAPK / Linkage analysis |
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| Research Abstract |
We previouly found that cultured smooth muscle cells from moyamoya patients produce excess amounts of prostaglandin E2 in response to interleukin-1 via activation of cyclooxygenase-2, leading to increase in vascular permeability. We also documented that moyamoya SMCs highly produce large amounts of vascular endothelial growth factor, a powerful vascular permeability factor as well as an angiogenic factor, by interleukin-1 stimulation. Up-regulated phosphorylation of p38 mitogen-activated kinase followed by activation of cyclooxygenase-2 in moyamoya smooth muscle cells contributed to the excess release of vascular endothelial growth factor and prostaglandin E2 by interleukin-1. We used cDNA tip to examine changes in mRNA expression of moyamoya SMC in response to IL-1. We also examined moyamoya SMC for the promotor region of COX-2 gene. Linkage analysis for familial moyamoya patients was further conducted to narrow down the matched locus. Higher responsiblity to inflammatory stimuli is considered to be a distinct feature of moyamoya smooth muscle cells, causing intimal thickening as well as an enhanced angiogenesis in moyamoya disease.
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