title: The role of endothelin-1 in the pathogenesis of pulmonary arterial hypertension.
abstract: The term pulmonary arterial hypertension (PAH) describes a rare group of diseases characterized by raised pulmonary vascular resistance, resulting from vascular remodelling in the pre-capillary resistance arterioles (< 100 mm). Left untreated, patients die from right heart failure, with a mortality approaching most serious cancers. Endothelin-1(ET-1) is not only a potent vasoconstrictor, but causes proliferation of many of the vascular cells involved in vascular remodelling. Although produced mainly by the vascular endothelium, other cells such as smooth muscle, fibroblasts and macrophages are known sources of ET-1 when these cells are challenged by relevant stimuli. Plasma ET-1 levels are raised in patients with PAH and correlate with important clinical outcomes. Furthermore, ET-1 receptor antagonism has been demonstrated to improve both morbidity and mortality in conditions associated with PAH. We review the literature supporting the role for ET-1 in the pathogenesis of PAH.
authors.affiliation: Department of Adult Intensive Care Unit, Royal Brompton Hospital, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London SW36LY, UK.
authors.forename: Dongmin
authors.initials: D
authors.lastname: Shao
authors.forename: John E S
authors.initials: JE
authors.lastname: Park
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Wort
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism / Q000502:physiology*; D065627:Familial Primary Pulmonary Hypertension; D006801:Humans; D006976:Hypertension, Pulmonary / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D017466:Receptors, Endothelin / Q000378:metabolism / Q000502:physiology*; D014655:Vascular Resistance / Q000502:physiology
chemical_list: D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D017466:Receptors, Endothelin