Role of endothelin-1 and its receptors, ET A and ET B , in the survival of human vascular endothelial cells.

Our previous work showed the presence of endothelin-1 (ET-1) receptors, ETA and ETB , in human vascular endothelial cells (hVECs). In this study, we wanted to verify whether ET-1 plays a role in the survival of hVECs via the activation of its receptors ETA and (or) ETB (ETA R and ETB R, respectively). Our results showed that treatment of hVECs with ET-1 prevented apoptosis induced by genistein, an effect that was mimicked by treatment with ETB R-specific agonist IRL1620. Furthermore, blockade of ETB R with the selective ETB R antagonist A-192621 prevented the anti-apoptotic effect of ET-1 in hVECs. However, activation of ETA receptor alone did not seem to contribute to the anti-apoptotic effect of ET-1. In addition, the anti-apoptotic effect of ETB R was found to be associated with caspase 3 inhibition and does not depend on the density of this type of receptor. In conclusion, our results showed that ET-1 possesses an anti-apoptotic effect in hVECs and that this effect is mediated, to a great extent, via the activation of ETB R. This study revealed a new role for ETB R in the survival of hVECs.