| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
Perctaneous transluminal coronary angioplasty and other vascular reconstructive procedure are effective treatments for ischemic heart disease. However, the incidense of postprocedural restenosis ranges from 30% to 50%. Therefore the mechanisms of restenosis should be elucidated and effective treatments for restenosis should be developed as soon as possible. AS one of the mechanisms of restenosis, it is thought that migration and proliferation of medial vascular smooth muscle cells and synthesis of extracellular matrix result in neointimal formation. Recently attention has focused on the role of adventitial cells in postprocedual restenosis. But little is known about their role, origin, and etc. Our object is to investigate their role and origin after balloon injury of rat carotid artery. At 2 days after injury, many proliferating cells labelled with BrdU were located around the adventitia lesion whereas the media demonstrated infrequent labelled cells or cell death. After that, labelle
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d cells were found to translocate to media and neointima lesion. These adventitial cells were expressing α-SM actin, SMemb, vimentin, ED1, Myf5 and MEF2 but no staining for MyoD and Myogenin. These migrating adventitial cells were ED1 positive ; ED2 positive cells never transmigrated into media and neointima. Therefore, these data suggest that adventitial myofibroblasts (positive for α-SM actin, SMemb and vimentin) were expressing muscle genes and may derive from hematogenous mononuclear leukocytes. To confirm this, we examined the cultured monocytes for production of muscle genes. Initially, almost all monocytes were positive for Myf5 and ED1 but were negative for MyoD, MEF2 and Myogenin. After 5 days in culture, these cells expressed MEF2 and some cells expressed α-SM actin and SMemb. These findings suggest that hematogenous mononuclear leukocytes can develop into myofibroblasts and contribute to neointimal formation and arterial remodelling after angioplasty. We would like to find the differentiation factors and their intracellular signal transduction of adventitial cells to elucidate the mechanism of restenosis and to develop effective treatments. Less
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