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Identification of Adventitial cells and Molecular Mechanisms of Phenotypic Modulation in the vasclar remodeling after bolloon injury

血管损伤后血管重塑中外膜细胞的鉴定和表型调节的分子机制

基本信息

批准号：
11670678
负责人：
TANIGUCHI Takahiro
金额：
$ 1.98万
依托单位：
Kobe University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670678/
关键词：
restenosis angioplasty vascular remodeling adventitial cell monocyte macrophage differentiation carotid arteries

项目摘要

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 … More 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

经皮冠状动脉腔内成形术和其他血管重建手术是治疗缺血性心脏病的有效方法。术后再狭窄发生率为30%~50%。因此，应尽快阐明再狭窄的发病机制，开发有效的再狭窄治疗方法。作为再狭窄的机制之一，中膜血管平滑肌细胞的迁移、增殖和细胞外基质的合成导致了新生内膜的形成。近年来，血管外膜细胞在术后再狭窄中的作用引起了人们的关注。但对它们的作用、来源等还知之甚少。我们的目的是探讨它们在大鼠颈动脉球囊损伤后的作用和来源。伤后2天，外膜周围可见大量BrdU标记的增殖细胞，而中膜细胞较少见标记细胞或细胞死亡。在那之后，LaBelle…更多的d细胞移位到中膜和新生内膜病变。这些外膜细胞表达α-SM肌动蛋白、SMemb、波形蛋白、ED1、MYF5和MEF2，而不表达MyoD和Mygenin。这些移行的外膜细胞呈ED1阳性；ED2阳性细胞从未向中层和新生内膜迁移。因此，这些数据表明外膜肌成纤维细胞(α-SM肌动蛋白、SMemb和波形蛋白阳性)表达肌肉基因，并可能来源于血源性单核细胞。为了证实这一点，我们检查了培养的单核细胞产生肌肉基因的情况。最初，几乎所有单核细胞Myf5和ED1阳性，MyoD、MEF2和Mygenin阴性。培养5d后，这些细胞表达MEF2，部分细胞表达α-SM肌动蛋白和SMemb。这些发现表明，血管成形术后，血源性单个核细胞可以发育成肌成纤维细胞，促进新生内膜形成和动脉重塑。我们希望寻找血管外膜细胞的分化因子及其细胞内信号转导途径，以阐明再狭窄的机制，并开发有效的治疗方法。较少