title: Monoamine oxidases are novel sources of cardiovascular oxidative stress in experimental diabetes.
abstract: Diabetes mellitus (DM) is widely recognized as the most severe metabolic disease associated with increased cardiovascular morbidity and mortality. The generation of reactive oxygen species (ROS) is a major event causally linked to the development of cardiovascular complications throughout the evolution of DM. Recently, monoamine oxidases (MAOs) at the outer mitochondrial membrane, with 2 isoforms, MAO-A and MAO-B, have emerged as novel sources of constant hydrogen peroxide (H2O2) production in the cardiovascular system via the oxidative deamination of biogenic amines and neurotransmitters. Whether MAOs are mediators of endothelial dysfunction in DM is unknown, and so we studied this in a streptozotocin-induced rat model of diabetes. MAO expression (mRNA and protein) was increased in both arterial samples and hearts isolated from the diabetic animals. Also, H2O2 production (ferrous oxidation - xylenol orange assay) in aortic samples was significantly increased, together with an impairment of endothelium-dependent relaxation (organ-bath studies). MAO inhibitors (clorgyline and selegiline) attenuated ROS production by 50% and partially normalized the endothelium-dependent relaxation in diseased vessels. In conclusion, MAOs, in particular the MAO-B isoform, are induced in aortas and hearts in the streptozotocin-induced diabetic rat model and contribute, via the generation of H2O2, to the endothelial dysfunction associated with experimental diabetes.
authors.affiliation: a Department of Pathophysiology, Faculty of Medicine, "Victor Babeş" University of Medicine and Pharmacy, 14, Tudor Vladimirescu st., 300173 Timişoara, Romania.|c Center for Translational Research and Systems Medicine, "Victor Babeş" University of Medicine and Pharmacy, Timişoara, Romania.
authors.forename: Adrian
authors.initials: A
authors.lastname: Sturza
authors.affiliation: a Department of Pathophysiology, Faculty of Medicine, "Victor Babeş" University of Medicine and Pharmacy, 14, Tudor Vladimirescu st., 300173 Timişoara, Romania.|c Center for Translational Research and Systems Medicine, "Victor Babeş" University of Medicine and Pharmacy, Timişoara, Romania.
authors.forename: Oana M
authors.initials: OM
authors.lastname: Duicu
authors.affiliation: b Department of Morphopathology, Faculty of Medicine, "Victor Babeş" University of Medicine and Pharmacy, Timişoara, Romania.
authors.forename: Adrian
authors.initials: A
authors.lastname: Vaduva
authors.affiliation: a Department of Pathophysiology, Faculty of Medicine, "Victor Babeş" University of Medicine and Pharmacy, 14, Tudor Vladimirescu st., 300173 Timişoara, Romania.|c Center for Translational Research and Systems Medicine, "Victor Babeş" University of Medicine and Pharmacy, Timişoara, Romania.
authors.forename: Maria D
authors.initials: MD
authors.lastname: Dănilă
authors.affiliation: a Department of Pathophysiology, Faculty of Medicine, "Victor Babeş" University of Medicine and Pharmacy, 14, Tudor Vladimirescu st., 300173 Timişoara, Romania.|c Center for Translational Research and Systems Medicine, "Victor Babeş" University of Medicine and Pharmacy, Timişoara, Romania.
authors.forename: Lavinia
authors.initials: L
authors.lastname: Noveanu
authors.affiliation: d Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Varró
authors.affiliation: a Department of Pathophysiology, Faculty of Medicine, "Victor Babeş" University of Medicine and Pharmacy, 14, Tudor Vladimirescu st., 300173 Timişoara, Romania.|c Center for Translational Research and Systems Medicine, "Victor Babeş" University of Medicine and Pharmacy, Timişoara, Romania.
authors.forename: Danina M
authors.initials: DM
authors.lastname: Muntean
mesh_terms: D000818:Animals; D001011:Aorta / Q000201:enzymology / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000201:enzymology / Q000209:etiology* / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000201:enzymology / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000201:enzymology / Q000503:physiopathology; D015870:Gene Expression; D007150:Immunohistochemistry; D008297:Male; D008995:Monoamine Oxidase / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology; D018384:Oxidative Stress / Q000502:physiology*; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013311:Streptozocin / Q000494:pharmacology
chemical_list: D017382:Reactive Oxygen Species; D013311:Streptozocin; D008995:Monoamine Oxidase
keywords: clorgyline; diabète sucré expérimental; dysfonction endothéliale; endothelial dysfunction; experimental diabetes mellitus; monoamine oxidases; monoamine oxydases; oxidative stress; selegiline; stress oxydatif; sélégiline