Anti-Inflammatory Effects of Endothelin Receptor Antagonists and their Importance for Treating Human Disease
Pp. 236-258 (23)
Matthias Barton, Philipp C. Nett, Kerstin Amann and Mauro M. Teixeira
Endothelin-1 (ET-1) is the main effector peptide of the endothelin family. Aside from being a potent endogenous vasoconstrictor and mitogen acting through its ETA receptors, it contributes to the regulation of immune mechanisms, inflammatory cell activation, and release of cytokines. Thereby, endothelin promotes the developement of a number of chronic disease conditions characterized by inflammtory activation, including atherosclerosis and chronic renal failure. Studies using orally active endothelin receptor antogonists have shown that the ETA receptor is mainly responsible for the immunomodulatory actions of endothelin. This review highlights recent findings in the field showing that the ET system, apart from being a marker and mediator of vascular injury, is directly involved in pathophysiology of these disease processes as an immunomodulatory factor. In this review, we summarize the current understanding of the mechanisms and signal transduction pathways triggered by ET-1 in inflammatory and immunomodulatory processes and discuss the findings of studies evaluating the use of selective and non-selective endothelin receptor antagonists in diseases associated with acute or chronic inflammatory activation, also discussing including the most recent clinical studies in the field using endothelin receptor antagonists.
Disease, drug therapy, human, clinical, inflammation, interleukin, autoimmune, scleroderma, diabetes, kidney, atherosclerosis, infection, chronic, endothelin receptor antagonist
Molecular Internal Medicine, University of Zurich, Switzerland