title: The role of endothelin system in cardiovascular disease and the potential therapeutic perspectives of its inhibition.
abstract: Since its identification in 1988 and the recognition of its primary role as a potent vasoconstrictor, endothelin has been extensively studied and is now considered as a ubiquitous protein, involved in important aspects of human homeostasis as well as in several pathophysiological pathways, mostly associated with cardiovascular disease. From an evolutionary point of view, endothelin consists a primitive molecule with the rare characteristic of being exactly the same in all mammals, thus permitting scientists to perform experiments in animals and doing predictions for humans. The understanding of its contribution to the genesis, evolution and maintenance of disease through activation of special receptor subtypes has led to the development of both selective and unselective receptor antagonists. Despite the disappointing results of these antagonists in the field of heart failure, almost from the initial animal trials of bosentan, a dual endothelin receptor antagonist, in pulmonary arterial hypertension, it has been demonstrated that the drug leads at least to hemodynamic and clinical improvement of the patients, thus receiving official approval for the management of this rare but eventually lethal disease. Resistant hypertension is another area where endothelin receptor blockers might potentially play a role, while the pathophysiological role of endothelin in atherosclerotic coronary artery disease is well-established and the relative research goes on. The main goal of this review is to describe the endothelin system and mostly to enlighten its role in pathophysiologic pathways, as well to state the relative research in the various fields of cardiovascular disease and also highlight its prognostic significance wherever there exists one.
authors.affiliation: Cardiology Department and Cardiac Catheterization Laboratory, Athens General Hospital G. Gennimatas, Athens, Greece. andreaskaoukis@yahoo.gr
authors.forename: Andreas
authors.initials: A
authors.lastname: Kaoukis
authors.forename: Spyridon
authors.initials: S
authors.lastname: Deftereos
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Raisakis
authors.forename: Georgios
authors.initials: G
authors.lastname: Giannopoulos
authors.forename: Georgios
authors.initials: G
authors.lastname: Bouras
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Panagopoulou
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Papoutsidakis
authors.forename: Michael W
authors.initials: MW
authors.lastname: Cleman
authors.forename: Christodoulos
authors.initials: C
authors.lastname: Stefanadis
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism / Q000503:physiopathology; D001281:Atrial Fibrillation / Q000378:metabolism / Q000503:physiopathology; D000077300:Bosentan; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D003324:Coronary Artery Disease / Q000378:metabolism / Q000503:physiopathology; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000097:blood / Q000502:physiology; D016232:Endothelins / Q000097:blood / Q000502:physiology*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy; D010666:Phenylpropionates / Q000494:pharmacology; D011237:Predictive Value of Tests; D011724:Pyridazines / Q000494:pharmacology; D017466:Receptors, Endothelin / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D016232:Endothelins; D010666:Phenylpropionates; D011724:Pyridazines; D017466:Receptors, Endothelin; D013449:Sulfonamides; C467894:ambrisentan; D000077300:Bosentan