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

经皮冠状动脉成形术和其他血管重建手术是缺血性心脏病的有效治疗方法。然而，术后再狭窄的发生率从30%到50%不等。因此，应尽快阐明再狭窄的发生机制，并开发有效的再狭窄治疗方法。作为再狭窄的机制之一，人们认为内侧血管平滑肌细胞的迁移和增殖以及细胞外基质的合成导致了新内膜的形成。近年来关注的焦点是外基质细胞在术后再狭窄中的作用。但人们对它们的作用、起源等知之甚少。目的探讨大鼠颈动脉球囊损伤后它们的作用和来源。在损伤后2天，许多带有BrdU标记的增殖细胞位于外膜病变周围，而培养基显示很少有标记细胞或细胞死亡。在此之后，发现更多的d细胞向中膜和新生内膜病变转移。这些上皮细胞表达α-SM肌动蛋白、SMemb、vimentin、ED1、Myf5和MEF2，但MyoD和Myogenin未染色。这些迁移的外基质细胞ED1阳性；ED2阳性细胞从未迁移到介质和新生内膜。因此，这些数据表明，外膜肌成纤维细胞（α-SM肌动蛋白、SMemb和vimentin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产生肌肉基因。最初，几乎所有的单核细胞Myf5和ED1呈阳性，而MyoD、MEF2和Myogenin呈阴性。培养5 d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，造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新内膜的形成和动脉重塑。我们希望通过研究外基质细胞的分化因子及其胞内信号转导来阐明再狭窄的发生机制，并寻求有效的治疗方法。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