The mechanism of intimal hyperplasia in vein graft
| Project/Area Number |
21591625
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Asahikawa Medical College |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Yukihiro 旭川医科大学, 医学部, 特任助教 (80540583)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 血管平滑筋細胞 / MMP-2 / 内膜肥厚 / 低酸素 / インテグリン / MMP2 / HIF1α / αvβ3インテグリン |
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| Research Abstract |
Many investigators have demonstrated that MMPs are important in smooth muscle cell (SMC) migration ex vivo and in neointimal hyperplasia (NH) lesion formation in animal model of injury. This study aim to demonstrate that MMP-2 have a critical role in the early NH lesion formation after arteriovenous (AV) access creation. Methods and Results : To determine MMP-2 is critical to early NH lesion formation after AV access creation, we created an AV fistula in mice by anastomosing the common carotid artery to the external jugular vein in an end-to-side fashion. After 3 weeks, MMP-2-/-mice have significantly less anastomotic NH lesion formation compared to the wild-type MMP-2+/+ mice confirming that MMP-2 activity is indeed critical to early neointimal hyperplasia in the setting of AV fistulae. And there is significant increase in the tissue levels of pro-MMP-2 and activated MMP-2 based the gelatin-substrate zymography. Also foundMMP-2-/-micehad noMMP-2 activityfonollowing AV fistula creation. These MMP-2-/-wemice did not have compensatory increase in the expression of MMP-9. We also demonstrated that like the human counterpart, the mouse NH lesion is predominantly SMCs (SM specific α-actin immunostaining) with minimal number of macrophages (Mac-3 immunostaining). In vitro, integrin αv, β3, and MMP-2 was up-regulated in SMC, when the cells cultured under hypoxic conditions. It seemed to have some relations between these molecules at its expressions. Conclusions : Ewasarly primary AV access failure due to anastomotic neointimal hyperplasia is associated with increased MMP-2-dependent SMC migration. This association is confirmed with the AV fistula mouse model, which demonstrated a significantly less anastomotic neointimal lesion formation in MMP-2-/-mice as compared to MMP-2+/+ mice.
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Report
(4 results)
Research Products
(13 results)
