| Project/Area Number |
04454355
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
脳神経外科学
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| Research Institution | TOKYO MEDICAL & DENTAL UNIVERSITY, SCHOOL OF MEDICINE |
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Principal Investigator |
AOYAGI Masaru TOKYO MEDICAL & DENTAL UNIVERSITY, SCHOOL OF MEDICINE, 医学部, 講師 (40134704)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUSHIMA Yoshiharu TOKYO MEDICAL & DENTAL UNIVERSITY, SCHOOL OF MEDICINE, 医学部, 助教授 (20134679)
YAMAMOTO Kiyotaka TOKYO METROPOLITAN INSTITUTE OF GERONTOLOGY, DEPARTMENT OF CELL BIOLOGY, 細胞生物部門, 主任研究員 (90073022)
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1993: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | moyamoya disease / vascular smooth muscle cells / PDGF / PDGF receptor / PDGF / TGF-β_1 |
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| Research Abstract |
Progressive stenosis or occlusion of bilateral internal carotid arteries by fibrocellular intimal thickening results in cerebral ischemia in moyamoya disease. We recently found that cultured smooth muscle cells (SMC) derived from arteries of patients with moyamoya disease responded poorly to serum mitogens, especially to platelet-derived growth factor (PDGF). In the present study, we investigated further the binding and processing of ^<125>I-PDGF, as well as down-regulation of the PDGF receptor in arterial SMC derived from patients with moyamoya disease. The specific binding sites of ^<125>I-PDGF were reduced significantly at both 4ﾟC and 22ﾟC on SMC from moyamoya disease compared with those from controls, though the apparent dissociation constant (Kd) were the same. Kinetics of ^<125>I-PDGF binding at 37ﾟC in cells from moyamoya disease showed fewer binding site and lower degradation per cell than in those from controls, though no difference was observed in either internalization or degradation of each receptor. When SMC were exposed to lower concentrations of nonlabeled PDGF at 37ﾟC, the percentage of remaining binding site on cells from moyamoya disease was significantly less than that from controls. This excess down-regulation of PDGF receptor in SMC from moyamoya disease may be interpreted as insufficient recycling or a decreased intracellular pool of the PDGF receptor. These results are closely correlated with the diminished proliferation responses to PDGF in SMC from moyamoya disease and provide evidence that functional alterrations in vascular cells are involved in the mechanism of development of intimal thickening in moyamoya disease.
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