Regulation of syndecan-4 expression with mechanical stress during the development of angioplasty-induced intimal thickening
Regulation of syndecan-4 expression with mechanical stress during the development of angioplasty-induced intimal thickening
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DOI：
10.1067/mva.2002.124364
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发表时间：
2002-08-01
影响因子：
4.3
通讯作者：
Chaikof, EL
中科院分区：
文献类型：
--
作者：
Li, L;Couse, TL;Chaikof, EL
在这项研究中，我们假设动脉壁的急性机械应变诱导syndecan-4表达的变化，这反过来又可能调节细胞事件，促进新生内膜形成。本研究通过体内外相关研究来确定：（1）球囊损伤大鼠颈动脉后，是否引起syndecan-4 mRNA和蛋白表达的时空调节性变化：（2）对培养的血管壁细胞施加双轴机械应变，是否调节syndecan-4 mRNA和蛋白的表达及其细胞表面分布和表面脱落;（3）脱落的syndecan-4直接影响细胞运动行为。我们观察到，syndecan-4的mRNA和蛋白表达的时间和空间的特定方式进行调节，这样syndecan-4的初始表达定位于外膜细胞，随后在新生内膜中表达。值得注意的是，在体外刺激分离的外膜成纤维细胞的机械拉伸协议，旨在模拟体内球囊损伤产生了syndecan-4的快速增加（4.3倍增加; P <0.001），这是伴随着增强的蛋白质脱落和局部粘连的解体。同样重要的是，脱落的syndecan-4，机械条件培养基诱导，似乎是负责外膜成纤维细胞的趋化反应（P = .005）。这些结果表明，机械应变紧密调节syndecan-4的表达，这可能，在一定程度上，提供了一种机制，激活肌成纤维细胞迁移到新生内膜的图尼卡外膜。
In this study, we postulated that acute mechanical strain of the arterial wall induces changes in syndecan-4 expression that in turn may modulate cellular events, which promote neointima formation. Correlative in vivo and in vitro studies were performed to determine whether: (1) balloon injury of the rat carotid artery induces spatially and temporally regulated changes in syndecan-4 messenger RNA (mRNA) and protein expression; (2) the application of biaxial mechanical strain to cultured vascular wall cells regulates the expression of syndecan-4 mRNA and protein and its cell surface distribution and surface shedding; and (3) shed syndecan-4 directly effects cell motility behavior. We observed that syndecan-4 mRNA and protein expression were regulated in a temporally and spatially specific manner, such that initial expression of syndecan-4 was localized to adventitial cells followed by later expression in the neointima. Notably, in vitro stimulation of isolated adventitial fibroblasts with a mechanical stretch protocol that was designed to mimic in vivo balloon injury produced a rapid increase in syndecan-4 (4.3-fold increase; P < .001) that was accompanied both by enhanced protein shedding and by the disassembly of focal adhesions. Also significant was that shed syndecan-4, induced with mechanically conditioned media, appeared to be responsible for a chemotactic response of adventitial fibroblasts (P = .005). These results indicate that mechanical strain tightly regulates syndecan-4 expression, which may, in part, provide a mechanism for the activation of myofibroblast migration from the tunica adventitia into the neointima.