Role of endothelin-1 and its receptors, ETA and ETB, in the survival of human vascular endothelial cells

Our previous work showed the presence of endothelin-1 (ET-1) receptors, ET_A and ET_B, 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 ET_A and (or) ET_B (ET_AR and ET_BR, respectively). Our results showed that treatment of hVECs with ET-1 prevented Apoptosis induced by genistein, an effect that was mimicked by treatment with ET_BR-specific agonist IRL1620. Furthermore, blockade of ET_BR with the selective ET_BR antagonist A-192621 prevented the anti-apoptotic effect of ET-1 in hVECs. However, activation of ET_A receptor alone did not seem to contribute to the anti-apoptotic effect of ET-1. In addition, the anti-apoptotic effect of ET_BR 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 ET_BR. This study revealed a new role for ET_BR in the survival of hVECs.

ETA receptor; ETB receptor; apoptose; apoptosis; cellules endothéliales vasculaires humaines; endothelin-1; endothéline-1; human vascular endothelial cells; récepteur ETA; récepteur ETB.