Approach to mechanism for post-operative pulmonary vein stenosis: experimental trials for adventitial hemorrhage-associated oxidative stress regulation

2015 Fiscal Year Final Research Report

• 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
• 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

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.

Free Research Field

病理学