title: The eNOS signalosome and its link to endothelial dysfunction.
abstract: Endothelial nitric oxide synthase (eNOS) plays an essential role in the regulation of endothelial function and acts as a master regulator of vascular tone and homeostasis through the generation of the gasotransmitter nitric oxide (NO). The complex network of events mediating efficient NO synthesis is regulated by post-translational modifications and protein-protein interactions. Dysregulation of these mechanisms induces endothelial dysfunction, a term often used to refer to reduced NO bioavailability and consequent alterations in endothelial function, that are a hallmark of many cardiovascular diseases. Endothelial dysfunction is linked to eNOS uncoupling, which consists of a switch from the generation of NO to the generation of superoxide anions and hydrogen peroxide. This review provides an overview of the eNOS signalosome, integrating past and recently described protein-protein interactions that have been shown to play a role in the modulation of eNOS activity with implications for cardiovascular pathophysiology. The mechanisms underlying eNOS uncoupling and clinically relevant strategies that were adopted to influence them are also discussed.
authors.affiliation: Institute for Vascular Signalling, Centre for Molecular Medicine, Johann Wolfgang Goethe University, Theodor Stern Kai 7, 60590, Frankfurt, Germany.
authors.forename: Mauro
authors.initials: M
authors.lastname: Siragusa
authors.affiliation: Institute for Vascular Signalling, Centre for Molecular Medicine, Johann Wolfgang Goethe University, Theodor Stern Kai 7, 60590, Frankfurt, Germany. fleming@em.uni-frankfurt.de.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Fleming
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III
keywords: Endothelial dysfunction; Endothelial nitric oxide synthase; Endothelium; Signalosome; Uncoupling