1995 Fiscal Year Final Research Report Summary
The Research for Regulation of Vascular Stenosis by Antisense Delivery System
| Project/Area Number |
06557071
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Thoracic surgery
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| Research Institution | Osaka University |
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Principal Investigator |
SAWA Yoshiki OSAKA UNIV., SCHOOL OF MEDICENE,ASSISTANT, 医学部, 助手 (00243220)
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| Co-Investigator(Kenkyū-buntansha) |
HAYSHI Kazuko OSAKA NATL.RESEARCH INST.HEAD OF LABO, 主任研究官
MASUDA Junichi NATL.CARDIOVASC.CENTER INST.HEAD OF LABO, 室長 (70173747)
TAKAHASHI Toshiki OSAKA UNIV.SCHOOL OF MEDICENE,ASSISTANT, 医学部, 助手 (50263257)
FUKUSSHIMA Norihide OSAKA UNIV.SCHOOL OF MEDICENE,ASSISTANT, 医学部, 助手 (30263247)
SHIRAKURA Ryota OSAKA UNIV., SCHOOL OF MEDICENE,PROFESSOR, 医学部, 教授 (00116047)
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| Project Period (FY) |
1994 – 1995
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| Keywords | Gene transfection / HVJ liposome method / Vein graft disease / Vein graft / Stent |
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| Research Abstract |
To elucidate the effect of stent as candidate for antisense carrier on vessels, we implanted intarvascular stent into rabbit descending thoracic aorta and analyzed the spatial chronological distribution of proliferation and phenotypes of smooth muscle cells in stent-implanted aorta. The results demonstrated that the regional effects on arterial wall by stenting leads to neointima formation through transient and regional proliferation and migration of smooth muscle cells and their phenotypic modulations. In situ hybridization clarified the expression of TGF-beta also transient in neointima imduced stent implantation into normal aorta. Meanwhile, in atherosclerotic aorta, neointima formation after stent implantation was more extensive and dedifferentiation of smooth muscle cells were not seen. In addition, we elucidated that macrophages and proteoglycans play important roles in regulating extracellular matrix accumulation in neointima after stent implantation in atherosclerotic aorta.
Nex
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t, we analyzed the mechanism of vein graft disease using rabbit autologous vein implantation model. Immunohistochemistry demonstrated neointima formation after the implantation followed dedifferentiation and proliferation of smooth muscle cells. To test the feasibility of ex vivo gene tranfection into the vein graft, we transferred reporter genes into vein graft using HVJ-liposome method. The genes were observed till 14 days after the implantation. Furthermore, to regulate the proliferation of smooth muscle cells, we transferred senescent cell-derived inhibitor 1 (sdil), known as a protein inhibiting cell proliferation. In sdil-taranfered vein grafts, neointima formation was less than control.
Thus, we demonstrated the feasibility of ex vivo gene transfection methods. Ex vivo transaction has two advantages over in vivo methods ; first, the influence of the vector carrying transferred gene was less than in vivo. Second, the efficacy of trnasfection is better because of direct trnasfection against targeted organs. Ex vivo transaction in surgical operation were expected in the future. Less
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