| Project/Area Number |
09557074
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
内分泌・代謝学
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| Research Institution | Chiba University |
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Principal Investigator |
SAITO Yasushi Chiba University,School of medicine,Professor, 医学部, 教授 (50101358)
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| Co-Investigator(Kenkyū-buntansha) |
HARUNO Akihiro Chiba University,School of Medicine,Professor, 研究員
BUJO Hideki Chiba University,University Hospital,Assistant, 医学部・付属病院, 助手 (80291300)
高橋 和男 千葉大学, 医学部, 医員
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥12,800,000 (Direct Cost: ¥12,800,000)
Fiscal Year 1999: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1998: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1997: ¥6,700,000 (Direct Cost: ¥6,700,000)
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| Keywords | intima / athevosclevosis / cytokine / re-stenosis / ECM / 平滑筋細胞 / 遺伝子発現 |
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| Research Abstract |
We developed a rat double-balloon injury model and studied the thickened neointima using immunohistochemical and RT-PCR methods. Fourteen days after the first balloon injury of the rat left common carotid artery, a second balloon injury was inflicted in the same place. Histochemical sections taken 14 days after the single- and double-balloon injuries were used for calculating intimal/medial (I/M) area ratios, as an indicator of neointimal formation, and were subjected to immunohistochemical staining. Total RNA was also purified from some arteries and mRNA expression of some extracellular matrices (ECM) and cytokine receptors related to ECM metabolism was estimated using the RT-PCR method. The I/M ratio in the rat double-balloon injury model (II) (1.84±0.62(mean±SE, n=5)) was significantly (p<0.05) higher than that in the single-balloon injury model (I) (1.30±0.19, n=10). The cell number per neointimal area was less in II than in I. As for the phenotype of smooth muscle cells, α-actin staining showed that the neointima of II consisted of more contractile form than synthetic, whereas that of I consisted of more synthetic form than contractile. The neointima of II was strongly stained with laminin and fibronectin, but that of I was stained only weakly. Consistent with these data, laminin and fibronectin mRNAs were markedly expressed in the neointima of II. Neointimas of both I and II were also stained positively with PDGF (α and β) and TGF-β (types I and II) receptors to the same extent. These results show: that ECM accumulation, particularly of laminin and fibronectin, characterizes the double-balloon injury model; that the marked accumulation of ECM in this model is due to a mechanism other than the PDGF or TGF-β signalling pathway; and that this model resembles the lesion of post-PTCA re-stenosis, and therefore provides the key for its investigation.
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