Endothelin-1 (ET-1) modulates several vascular functions and plays an important role in the pathogenesis of insulin resistance. However, its role in the pathogenesis of impaired angiogenesis observed under insulin resistance conditions is not known. In the present study, we addressed this issue by analyzing the effect of ET-1 in human umbilical vein endothelial cells (HUVEC) on i) insulin-induced phosphorylation of two protein kinases involved in angiogenesis, Akt and ERK1/2, and on ii) insulin-induced angiogenesis in two in vitro models, those of Matrigel and of fibroblast/endothelial co-culture. Both insulin (100 ng/ml) and ET-1 (10 nmol/l) dose-dependently increased the phosphorylation of Akt and ERK1/2. Pre-treatment with ET-1 did not suppress the insulin-induced Akt and ERK1/2 phosphorylation. In the two in vitro models of angiogenesis, ET-1 did not inhibit insulin-induced angiogenesis. From these data we conclude that in vitro, at the times and at the concentrations examined, ET-1 does not impair insulin-induced angiogenesis.

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