Rubina Kseniya, Kalinina Natalia, Potekhina Alexandra, Efimenko Anastasia, Semina Ekaterina, Poliakov Alexei, Wilkinson David G, Parfyonova Yelena, Tkachuk Vsevolod
Department of Biological and Medical Chemistry, Faculty of Fundamental Medicine, Lomonosov Moscow State University, 31-5, Lomonosovsky av., Moscow, 119192, Russia.
Angiogenesis. 2007;10(3):183-95. doi: 10.1007/s10456-007-9072-2. Epub 2007 May 8.
Our previous studies have revealed the abundant expression of T-cadherin--a glycosylphosphatidylinositol (GPI)-anchored member of cadherin superfamily--in endothelial and mural cells in the heart and vasculature. The upregulation of T-cadherin in vascular proliferative disorders such as atherosclerosis and restenosis suggests the involvement of T-cadherin in vascular growth and remodeling. However, the functional significance of this molecule in the vasculature remains unknown. The effect of T-cadherin on angiogenesis in vivo was evaluated using Matrigel implant model. We demonstrate that T-cadherin overexpression in L929 cells injected in Matrigel inhibits neovascularization of the plug. In vitro T-cadherin inhibits the directional migration of endothelial cells, capillary growth, and tube formation but has no effect on endothelial cell proliferation, adhesion, or apoptosis in vitro. These data suggest that T-cadherin expressed in the stroma could act as a negative guidance cue for the ingrowing blood vessels and thus could have an important potential therapeutic application.
我们之前的研究表明，T-钙黏蛋白（一种糖基磷脂酰肌醇（GPI）锚定的钙黏蛋白超家族成员）在心脏和血管系统的内皮细胞及壁细胞中大量表达。在动脉粥样硬化和再狭窄等血管增殖性疾病中T-钙黏蛋白上调，提示其参与血管生长和重塑。然而，该分子在血管系统中的功能意义仍不清楚。利用基质胶植入模型评估了T-钙黏蛋白对体内血管生成的影响。我们证明，注射到基质胶中的L929细胞中T-钙黏蛋白过表达会抑制植入物的新生血管形成。在体外，T-钙黏蛋白抑制内皮细胞的定向迁移、毛细血管生长和管腔形成，但对体外内皮细胞增殖、黏附或凋亡无影响。这些数据表明，基质中表达的T-钙黏蛋白可能作为新生血管向内生长的负向引导信号，因此可能具有重要的潜在治疗应用价值。
