Wallner K, Sharifi B G, Shah P K, Noguchi S, DeLeon H, Wilcox J N
Atherosclerosis Research Center, Division of Cardiology, Burns and Allen Research Institute, UCLA School of Medicine, Los Angeles, California, USA.
J Am Coll Cardiol. 2001 Feb;37(2):655-61. doi: 10.1016/s0735-1097(00)01117-7.
The purpose of this study was to determine the temporospatial expression of tenascin-C (TnC) in balloon-injured rat and porcine arteries.
Recent studies suggest that cell migration, in addition to cell proliferation, is a critical component of neointima formation after vascular injury. We have previously shown that adventitial myofibroblasts synthesize growth factors that contribute to the formation of neointima after arterial injury. We have also shown that the extracellular matrix protein, TnC, regulates cell migration. Consequently, we investigated the temporospatial expression of TnC by myofibroblasts after vascular injury.
In situ hybridization and immunohistochemistry were used to investigate the temporospatial expression of TnC in injured arteries. Northern and Western blots were used to determine the in vitro expression of TnC.
In situ hybridization revealed that the major site of TnC expression early after vascular injury was the adventitial myofibroblasts. Immunohistochemical staining demonstrated that TnC expression began in adventitial myofibroblasts three days after injury. Tenascin-C expression, however, did not persist in this region. Rather, it moved progressively across the vascular wall toward the luminal surface. By one week, TnC expression reached the developing neointima. In vitro, myofibroblasts did not express TnC mRNA under basal conditions. In contrast, angiotensin II and PDGF-BB, factors that have been implicated in remodeling of balloon-injured arteries, markedly upregulated TnC mRNA.
Tenascin-C is expressed in response to balloon injury. Tenascin-C expression begins with adventitial myofibroblasts. Over a period of 7 to 14 days, expression moves progressively across the vessel wall to the neointima. We hypothesize that adventitial myofibroblasts are actively involved in the formation of neointima and that TnC facilitates migration of these cells during adventitial remodeling.
本研究旨在确定腱生蛋白-C（TnC）在球囊损伤的大鼠和猪动脉中的时空表达。
最近的研究表明，除细胞增殖外，细胞迁移是血管损伤后内膜形成的关键组成部分。我们之前已经表明，外膜肌成纤维细胞合成有助于动脉损伤后内膜形成的生长因子。我们还表明，细胞外基质蛋白TnC调节细胞迁移。因此，我们研究了血管损伤后肌成纤维细胞中TnC的时空表达。
采用原位杂交和免疫组织化学方法研究损伤动脉中TnC的时空表达。采用Northern印迹和Western印迹法测定TnC的体外表达。
原位杂交显示，血管损伤后早期TnC表达的主要部位是外膜肌成纤维细胞。免疫组织化学染色表明，TnC表达在损伤后三天开始于外膜肌成纤维细胞。然而，腱生蛋白-C的表达并未在该区域持续存在。相反，它逐渐穿过血管壁向管腔表面移动。到一周时，TnC表达到达正在形成的内膜。在体外基础条件下，肌成纤维细胞不表达TnC mRNA。相比之下，血管紧张素II和血小板衍生生长因子BB（PDGF-BB）这两种与球囊损伤动脉重塑有关的因子，显著上调了TnC mRNA。
腱生蛋白-C在球囊损伤后表达。腱生蛋白-C的表达始于外膜肌成纤维细胞。在7至14天的时间内，表达逐渐穿过血管壁到达内膜。我们推测外膜肌成纤维细胞积极参与内膜的形成，并且TnC在促进这些细胞在外膜重塑过程中的迁移。
