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

• Published in: Canadian journal of physiology and pharmacology Vol. 95; no. 10; p. 1298
• Main Authors: Mikhail, Marianne, Vachon, Pierre H, D’Orléans-Juste, Pedro, Jacques, Danielle, Bkaily, Ghassan
• Format: Journal Article
• Language: English
• Published: Ottawa Canadian Science Publishing NRC Research Press 01.10.2017
• Subjects: Apoptosis; Endothelial cells; Endothelin 1; Endothelins; Endothelium; Pharmacology; Physiology; Vein & artery diseases; Canada
• ISSN: 0008-4212; 1205-7541; 1205-7541
• DOI: 10.1139/cjpp-2017-0412

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 (ETAR and ETBR, respectively). Our results showed that treatment of hVECs with ET-1 prevented apoptosis induced by genistein, an effect that was mimicked by treatment with ETBR-specific agonist IRL1620. Furthermore, blockade of ETBR with the selective ETBR 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 ETBR 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 ETBR. This study revealed a new role for ETBR in the survival of hVECs.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 (ETAR and ETBR, respectively). Our results showed that treatment of hVECs with ET-1 prevented apoptosis induced by genistein, an effect that was mimicked by treatment with ETBR-specific agonist IRL1620. Furthermore, blockade of ETBR with the selective ETBR 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 ETBR 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 ETBR. This study revealed a new role for ETBR in the survival of hVECs.