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

• Published in: Canadian journal of physiology and pharmacology Vol. 95; no. 10; pp. 1298 - 1305
• Main Authors: Mikhail, Marianne, Vachon, Pierre H., D’Orléans-Juste, Pedro, Jacques, Danielle, Bkaily, Ghassan
• Format: Journal Article
• Language: English
• Published: Canada 01.10.2017
• Subjects: Apoptosis - drug effects; Caspase 3 - metabolism; Cell Survival - drug effects; Cells, Cultured; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Endothelial Cells - pathology; Endothelin A Receptor Antagonists - pharmacology; Endothelin B Receptor Antagonists - pharmacology; Endothelin-1 - pharmacology; Genistein - toxicity; Humans; Receptor, Endothelin A - agonists; Receptor, Endothelin A - metabolism; Receptor, Endothelin B - agonists; Receptor, Endothelin B - metabolism; Signal Transduction - drug effects; ETB receptor; human vascular endothelial cells; ETA receptor; cellules endothéliales vasculaires humaines; récepteur ETB; apoptosis; récepteur ETA; endothéline-1; apoptose; endothelin-1
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/cjpp-2017-0412

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 A R and ET B 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 ET B R-specific agonist IRL1620. Furthermore, blockade of ET B R with the selective ET B R 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 B 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 ET B R. This study revealed a new role for ET B R in the survival of hVECs.