1993 Fiscal Year Final Research Report Summary
Research for the mechanism of development of intimal thickening in moyamoya disease.
| Project/Area Number |
04670878
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Cerebral neurosurgery
|
|---|
| Research Institution | Tokyo Metropolitan Institute of Gerontology |
|---|
Principal Investigator |
FUKAI Naomi Tokyo Metro. Inst. Geront. Dept. Cell Biol. Researcher, 細胞生物, 研究員 (60134681)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SAKAMOTO Hiroshi Tokyo Metro. Inst. Geront. Dept. Cell Biol. Researcher, 細胞生物, 研究員 (70150224)
YAMAMOTO Kiyotaka Tokyo Metro. Inst. Geront. Dept. Cell Biol. Senior Researcher, 細胞生物, 主任研究員 (90073022)
|
|---|
| Project Period (FY) |
1992 – 1993
|
| Keywords | Moyamoya disease / Smooth muscle cells / Crll proliferation / Growth factors / PDGF receptor |
|---|
| Research Abstract |
Moyamoya disease is a progressive cerebrovascular occusive disease that occurs frequently in children. The etiology is unknown. From the assumption that functional alterations in vascular cells are responsible for development of intimal thickening in moyamoya disease, we examined biological characteristics and the proliferative response of smooth muscle cells (SMC) derived from arteries of patients with moyamoya disease. Moyaoya SMC had a normal human diploid karyotype. The population doubling time a the early PDL was significantly longer in moyamoya SMC than cntrol. The reduced stimulation of DNA synthesis by PDGF was retained with moyamoya SMC throughout the life span in vitro. The specific binding sites of ^<125>I-PDGF were reduced significantly at both 4ﾟC and 22ﾟC on moyamoya SMC compared with those of control SMC, thugh the apparent dissociation constant were the same. Kinetics of ^<125>I-PDGF binding at 37ﾟC in moyamoya cells showed fewer binding sites (less than 1/3 of controls) and lower degrada6tion per cell than in those of 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 sites on moyamoya cells was significantly less than that from controls. This excess down-regulation of PDGF receptor in moyamoya SMC may be interpreted as insufficient recycling or a decreased intracellular pool of the PDGF receptor. These esults are closely correlated with the diminished proliferation responses to PDGF in moyamoya SMC and provide evidence that functional alterations in vascular cells are involved in the mechanism of development of intimal thickening in moyamoya disease.
|
