Ziche M, Morbidelli L, Donnini S, Ledda F
Department of Preclinical and Clinical Pharmacology, Mario Aiazzi Mancini, University of Florence, Italy.
J Cardiovasc Pharmacol. 1995;26 Suppl 3:S284-6.
We investigated endothelin-1 and -3 (ET-1, ET-3) effects on proliferation and migration of endothelial cells isolated from bovine adrenal capillaries (BACEs) and from human umbilical veins (HUVECs). 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 selective agonist for the ETB receptor ET(16-21) showed the same effects as ET-1 and ET-3 on proliferation and migration in both cell lines. The ETB receptor antagonist IRL 1038 (1 microM) blocked the migration induced by both ET-3 and ET[16-21], whereas the ETA receptor antagonist BQ 123 (1 microM) was ineffective. We conclude that endothelins, by favoring endothelial cell growth and mobilization, can contribute to neovascularization through an autocrine mechanism that requires ETB receptor activation.
我们研究了内皮素 -1 和 -3（ET-1、ET-3）对从牛肾上腺毛细血管（BACEs）和人脐静脉（HUVECs）分离的内皮细胞增殖和迁移的影响。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 浓度时具有最大效应。ET-1 和 ET-3 还以剂量依赖性方式刺激 BACE 和 HUVEC 的迁移。ETB 受体的选择性激动剂 ET(16-21) 在两种细胞系中对增殖和迁移表现出与 ET-1 和 ET-3 相同的作用。ETB 受体拮抗剂 IRL 1038（1 μM）可阻断 ET-3 和 ET[16-21] 诱导的迁移，而 ETA 受体拮抗剂 BQ 123（1 μM）则无效。我们得出结论，内皮素通过促进内皮细胞生长和迁移，可通过一种需要 ETB 受体激活的自分泌机制促进新血管形成。
