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

经皮冠状动脉腔内成形术和其他血管重建术是治疗缺血性心脏病的有效方法。然而，术后再狭窄的发生率为30%~ 50%。因此，应尽快阐明再狭窄的发生机制，开发有效的治疗方法。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。但其作用、来源等尚不清楚，本研究旨在探讨其在大鼠颈动脉球囊损伤后的作用及来源。损伤后2天，许多增殖细胞标记BrdU位于周围的外膜病变，而媒体表现出罕见的标记细胞或细胞死亡。在那之后，拉贝尔 关于我们 d细胞移位至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、ED 1、Myf 5和MEF 2，但不表达MyoD和Myogenin。这些迁移的外膜细胞呈ED 1阳性; ED 2阳性细胞从未迁移到中膜和新生内膜中。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，可能来源于血源性单核白细胞。为了证实这一点，我们检查了培养的单核细胞的肌肉基因的产生。最初，几乎所有单核细胞对Myf 5和ED 1呈阳性，但对MyoD、MEF 2和Myogenin呈阴性。培养5天后，这些细胞表达MEF 2，一些细胞表达α-SM肌动蛋白和SMemb。这些结果表明，血单核白细胞可以发育成肌成纤维细胞，并有助于血管成形术后的新生内膜形成和动脉重塑。因此，我们希望通过研究血管外膜细胞的分化因子及其细胞内信号转导机制，阐明血管再狭窄的发生机制，并为血管再狭窄的治疗提供新的思路。少

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