Project/Area Number |
26670190
|
Research Category |
Grant-in-Aid for Challenging Exploratory Research
|
Allocation Type | Multi-year Fund |
Research Field |
Experimental pathology
|
Research Institution | The University of Tokushima |
Principal Investigator |
SAKASHITA Naomi 徳島大学, 大学院医歯薬学研究部, 教授 (90284752)
|
Co-Investigator(Kenkyū-buntansha) |
HORIGUCHI Hidehisa 徳島大学, 大学院医歯薬学研究部, 准教授 (40304505)
NISHITSUJI Kazuchika 徳島大学, 大学院医歯薬学研究部, 助教 (40532768)
|
Project Period (FY) |
2014-04-01 – 2016-03-31
|
Project Status |
Completed (Fiscal Year 2015)
|
Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | ヘムオキシゲナーゼ1 / 平滑筋 / 酸化ストレス / マクロファージ / 粥状動脈硬化 / 内膜肥厚 / 血管平滑筋 / 術後性肺静脈狭窄症 / 内膜増殖 |
Outline of Final Research Achievements |
We examined neointimal proliferation under situation of hemeoxygenase-1 (HO-1) insufficiency. Smooth muscle cell with hemin treatment showed oxidative stress, temporal overexpression of ERK, NF-κB, STAT3, HO-1 and smooth muscle cell proliferation/migration. Immunohistochemistry revealed strong immunoreactivity of oxidative stress marker, 8OHDG, to the proliferated neointima of the post-operative stenosed pulmonary vein. However, no HO-1 was detected in pulmonary vein. These data suggest that HO-1 expression in pulmonary vein prevented hemin-induced oxidative stress and smooth muscle proliferation. To address this hypothesis, effect of HO-1 inhibitor ZnPP on hemin-induced smooth muscle proliferation was examined but ZnPP exerted no effect on smooth muscle cells proliferation. Because our hypothesis did not confirmed, we next examined role of HO-1 on atherosclerosis. We found foamy transformed macrophages in atheromatous plaque failed to express HO-1 and may promote plaque rupture.
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