1993 Fiscal Year Final Research Report Summary
Effects of extracellular matrix on changes of phenotype and gene expression in vascular smooth muscle cells
| Project/Area Number |
04670371
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
内科学一般
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| Research Institution | Chiba University |
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Principal Investigator |
MURANO Shunichi Chiba University, 2nd Dep. Int. Medicine Instructor, 医学部・附属病院, 助手 (50231634)
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| Co-Investigator(Kenkyū-buntansha) |
MORISAKI Nobuhiro Chiba University, 2nd Dep. Int. Medicine Assistant Professor, 医学部・附属病院, 講師 (40174411)
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| Project Period (FY) |
1992 – 1993
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| Keywords | Basculr smooth muscle cell / Endothelial denudation / Smooth muscle cell phenotype / Atherosclerosi / PDGF / Tumor necrosis factor / Extra cellular matrix |
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| Research Abstract |
We have examined effects of endothelial denudatio of phenotype cange of vasclar smooth muscle cells(SMC). Outgrowth rate of SMC from explants of aorta 2 or 5 days after denudation was much higher than that from untreated aorta. Scavenger pathway for acetylated low density lipoprotein and autocrine secretion of growth stimulator(s) were also observed inSMC from the aorta 5 days after denudation but not in SMC from untreated aorta. These acquired pathological ahcracters were similar to those of intimal SMC from atherosclerotic lesions. These results suggest that critical point of the phenotype change is at very early time after the treatment and it occurs within the aortic media before formation of neo-intima. another experimants revealed that SMCfrom aorta of diabetic rabbits expressed PDGF beta and the SMC showed rapid growthrate responded to PDGF-AB, PDGF-BB or whole serum. The other experiments showed that tumor necrosis factor-alpha stimulated SMC to change their phenotype from contractile to synthetic type. These data suggest that early response of medial SMC to intimal injury must ve very important to regulate the following steps to formation of atherosclerosis. We are now engaging in experiments to clarify changes of gene expression in the initial step of phenotype change after endothelial denudation. After that, effects of interaction between SMC and extracellular matrix on the phenotype of SMC will be further elucidated to assess possibilities to regulate the early step of phenotype change.
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