Morbidelli L, Orlando C, Maggi C A, Ledda F, Ziche M
Department of Preclinical, University of Florence, Italy.
Am J Physiol. 1995 Aug;269(2 Pt 2):H686-95. doi: 10.1152/ajpheart.1995.269.2.H686.
The growth and migration of endothelial cells are the prerequisites for vascular remodeling. The effects of endothelin (ET)-1 and -3 (ET-1, ET-3) on the proliferation and migration of endothelial cells isolated from bovine adrenal capillaries (BACE) and human umbilical veins (HUVEC) have been investigated. Cell proliferation (measured as DNA synthesis and as total cell number) and migration were significantly increased by ET-1 and ET-3. Dose-dependent proliferation was produced by ET-1 and ET-3 in both cell lines, with maximal effects at 0.1 nM concentration. ET-1 and ET-3 also stimulated BACE and HUVEC mobilization in a dose-dependent manner. The maximal responses were obtained at 10 nM concentration in both BACE and HUVEC. The full agonist for the ETB receptor, ET-(16--21), was able to reproduce the effects of ET on proliferation and migration of both cell lines. Modification of ET-(16--21) at Leu17 and Ile19 and amidation of the COOH-terminal were accompanied by loss of activity. The ETB-receptor antagonist IRL-1038 blocked the migration induced by ET-3 and ET-(16--21), whereas the ETA-receptor antagonist BQ-123 was not effective. We conclude that ETs, by favoring endothelial cell growth and mobilization, can contribute to neovascularization through an autocrine mechanism that requires ETB-receptor activation.
内皮细胞的生长和迁移是血管重塑的前提条件。研究了内皮素（ET）-1和-3（ET-1、ET-3）对从牛肾上腺毛细血管（BACE）和人脐静脉（HUVEC）分离的内皮细胞增殖和迁移的影响。ET-1和ET-3显著增加了细胞增殖（以DNA合成和总细胞数衡量）和迁移。ET-1和ET-3在两种细胞系中均产生剂量依赖性增殖，在0.1 nM浓度时作用最大。ET-1和ET-3还以剂量依赖性方式刺激BACE和HUVEC的动员。在BACE和HUVEC中，10 nM浓度时均获得最大反应。ETB受体的完全激动剂ET-(16-21)能够重现ET对两种细胞系增殖和迁移的作用。在Leu17和Ile19处对ET-(16-21)进行修饰以及对COOH末端进行酰胺化伴随着活性丧失。ETB受体拮抗剂IRL-1038可阻断ET-3和ET-(16-21)诱导的迁移，而ETA受体拮抗剂BQ-123则无效。我们得出结论，ETs通过促进内皮细胞生长和动员，可通过一种需要ETB受体激活的自分泌机制促进新生血管形成。
