Effect of thalidomide affecting VEGF secretion, cell migration, adhesion and capillary tube formation of human endothelial EA.hy 926 cells
Effect of thalidomide affecting VEGF secretion, cell migration, adhesion and capillary tube formation of human endothelial EA.hy 926 cells
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DOI：
10.1016/j.lfs.2005.10.016
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发表时间：
2006-04-25
期刊：
影响因子：
6.1
通讯作者：
Stepien, H
中科院分区：
文献类型：
--
作者：
Komorowski, J;Jerczynska, H;Stepien, H
血管生成是一个多步骤的过程，受促血管生成细胞因子的精确调节，其刺激内皮细胞迁移、增殖和分化以形成新的毛细血管。过度的血管发育和血管重塑出现在银屑病、类风湿性关节炎、糖尿病视网膜病变和实体瘤形成中。沙利度胺[α-（N-邻苯二甲酰亚胺）-戊二酰亚胺]是一种有效的血管生成抑制剂，但其抑制作用的机制尚不清楚。该研究的目的是调查沙利度胺的潜在影响的几个步骤的血管生成，使用体外模型。我们评价了沙利度胺对人内皮细胞系EA.hy926的VEGF分泌、细胞迁移、粘附以及毛细血管形成的影响。沙利度胺在0.01 μ M和10 μ M的浓度下抑制VEGF分泌到上清液中，减少形成的毛细管的数量，并增加细胞与胶原的粘附。沙利度胺在0.01 μ M浓度下的给药增加了细胞迁移，而在10 μ M时，它减少了细胞迁移。沙利度胺浓度从0.1 μ M到10 μ M没有改变72小时细胞培养物的细胞增殖。我们认为沙利度胺的抗血管生成作用是由于直接抑制VEGF的分泌和毛细血管的形成以及对EA.hy926细胞迁移和粘附的免疫调节作用。(c)2005年爱思唯尔公司All rights reserved.
Angiogenesis, new blood vessel formation, is a multistep process, precisely regulated by pro-angiogenic cytokines, which stimulate endothelial cells to migrate, proliferate and differentiate to form new capillary microvessels. Excessive vascular development and blood vessel remodeling appears in psoriasis, rheumatoid arthritis, diabetic retinopathy and solid tumors formation. Thalidomide [alpha-(N-phthalimido)-glutarimide] is known to be a potent inhibitor of angiogenesis, but the mechanism of its inhibitory action remains unclear. The aim of the study was to investigate the potential influence of thalidomide on the several steps of angiogenesis, using in vitro models. We have evaluated the effect of thalidomide on VEGF secretion, cell migration, adhesion as well as in capillary formation of human endothelial cell line EA.hy 926. Thalidomide at the concentrations of 0.01 mu M and 10 mu M inhibited VEGF secretion into supernatants, decreased the number of formed capillary tubes and increased cell adhesion to collagen. Administration of thalidomide at the concentration of 0.01 mu M increased cell migration, while at 10 mu M, it decreased cell migration. Thalidomide in concentrations from 0.1 mu M to 10 mu M did not change cell proliferation of 72-h cell cultures. We conclude that anti-angiogenic action of thalidomide is due to direct inhibitory action on VEGF secretion and capillary microvessel formation as well as immunomodulatory influence on EA.hy 926 cells migration and adhesion. (c) 2005 Elsevier Inc. All rights reserved.