Cardioprotective signaling by endothelin.
The endothelin axis promotes vasoconstriction, suggesting that antagonists of endothelin signaling might be useful in treatment of heart failure. However, promising results from animal trials have not been recapitulated in heart failure patients. Here we review the role of major signaling pathways in the heart that are involved in cell survival initiated by ET-1. These pathways include mitogen-activated protein kinase, phosphatidyl inositol-1,4,5-triphosphate kinase (PI3K-AKT), nuclear factor-kappaB (NF-kappaB), and calcineurin signaling. A better understanding of endothelin-mediated signaling in cardiac cell survival may allow a reevaluation of endothelin receptor antagonists (ETRAs) in the treatment of heart failure.
Schorlemmer
Anita
A
Department of Medicine, Center of Cardiovascular Research, John A Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, USA.
Matter
Michelle L
ML
Shohet
Ralph V
RV
D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D002986:Clinical Trials as Topic; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism*; D016232:Endothelins / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D019317:Evidence-Based Medicine; D048049:Extracellular Signal-Regulated MAP Kinases; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D044022:Receptor, Endothelin A / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000378:metabolism; D017466:Receptors, Endothelin / Q000378:metabolism
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D016232:Endothelins; D016328:NF-kappa B; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; D019703:Calcineurin