Endothelin-3 mediated proliferation in wounded human umbilical vein endothelial cells

An in vitro model of endothelial cell injury was used to investigate the role of endothelins and related peptides in endothelial repair. Endothelin-3 (10-100 nM) enhanced wound repair over an 18 h period by promoting proliferation, an effect not inhibited by the specific ETA receptor antagonist BQ-123 (100 nM) or the mixed ETA/ETB antagonist PD142893 (10 microM). Like endothelin-3, the ETB selective agonists [Ala1,3,11,15]endothelin-1 and sarafotoxin S6c were able to enhance wound repair over the same dose range. Neither endothelin-1 nor endothelin-2, however, had any effect on endothelial cell wound healing. Inhibition of cyclo-oxygenase or neutralisation of basic fibroblast growth factor did not inhibit this endothelin-3-mediated event. These results suggest that endothelin-3 might have a direct role in endothelial cell proliferation as a response to injury which is not mediated by either of the currently defined ETA and ETB receptors.