title: Tackling endothelial dysfunction by modulating NOS uncoupling: new insights into its pathogenesis and therapeutic possibilities.
abstract: Endothelial nitric oxide synthase (eNOS) serves as a critical enzyme in maintaining vascular pressure by producing nitric oxide (NO); hence, it has a crucial role in the regulation of endothelial function. The bioavailability of eNOS-derived NO is crucial for this function and might be affected at multiple levels. Uncoupling of eNOS, with subsequently less NO and more superoxide generation, is one of the major underlying causes of endothelial dysfunction found in atherosclerosis, diabetes, hypertension, cigarette smoking, hyperhomocysteinemia, and ischemia/reperfusion injury. Therefore, modulating eNOS uncoupling by stabilizing eNOS activity, enhancing its substrate, cofactors, and transcription, and reversing uncoupled eNOS are attractive therapeutic approaches to improve endothelial function. This review provides an extensive overview of the important role of eNOS uncoupling in the pathogenesis of endothelial dysfunction and the potential therapeutic interventions to modulate eNOS for tackling endothelial dysfunction.
authors.affiliation: Maastricht Univ. Medical Centre, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands.
authors.forename: Rinrada
authors.initials: R
authors.lastname: Kietadisorn
authors.forename: Rio P
authors.initials: RP
authors.lastname: Juni
authors.forename: An L
authors.initials: AL
authors.lastname: Moens
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism* / Q000503:physiopathology; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D004795:Enzyme Stability / Q000187:drug effects; D006801:Humans; D009569:Nitric Oxide / Q000819:agonists / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D014652:Vascular Diseases / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III