title: Monoamine Oxidase Is Overactivated in Left and Right Ventricles from Ischemic Hearts: An Intriguing Therapeutic Target.
abstract: Growing evidence indicates that reactive oxygen species (ROS) may play a key role in human heart failure (HF). Monoamine oxidase (MAO) is emerging as a major ROS source in several cardiomyopathies. However, little is known about MAO activity in human failing heart and its relationship with redox imbalance. Therefore, we measured MAO activity in the left (LV) and in the right (RV) ventricle of human nonfailing (NF) and in end-stage ischemic (IHD) and nonischemic failing hearts. We found that both MAO isoforms (MAO-A/B) significantly increased in terms of activity and expression levels only in IHD ventricles. Catalase and aldehyde dehydrogenase-2 activities (ALDH-2), both implicated in MAO-catalyzed catecholamine catabolism, were significantly elevated in the failing LV, whereas, in the RV, statistical significance was observed only for ALDH-2. Oxidative stress markers levels were significantly increased only in the failing RV. Actin oxidation was significantly elevated in both failing ventricles and related to MAO-A activity and to functional parameters. These data suggest a close association between MAO-A-dependent ROS generation, actin oxidation, and ventricular dysfunction. This latter finding points to a possible pathogenic role of MAO-A in human myocardial failure supporting the idea that MAO-A could be a new therapeutic target in HF.
authors.affiliation: Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), Center of Molecular Medicine (CIMMBA), University of Florence, Florence, Italy.
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Manni
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
authors.forename: Stefania
authors.identifier: 0000-0002-5803-1198
authors.initials: S
authors.lastname: Rigacci
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Borchi
authors.affiliation: Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), Center of Molecular Medicine (CIMMBA), University of Florence, Florence, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Bargelli
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
authors.forename: Caterina
authors.identifier: 0000-0001-6632-7493
authors.initials: C
authors.lastname: Miceli
authors.affiliation: Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Rome, Italy.
authors.forename: Carla
authors.identifier: 0000-0002-3716-4303
authors.initials: C
authors.lastname: Giordano
authors.affiliation: Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), Center of Molecular Medicine (CIMMBA), University of Florence, Florence, Italy.
authors.forename: Laura
authors.identifier: 0000-0002-8423-0860
authors.initials: L
authors.lastname: Raimondi
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
authors.forename: Chiara
authors.identifier: 0000-0003-3190-3539
authors.initials: C
authors.lastname: Nediani
mesh_terms: D000199:Actins / Q000378:metabolism; D000368:Aged; D000071396:Aldehyde Dehydrogenase, Mitochondrial / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D006333:Heart Failure / Q000201:enzymology / Q000473:pathology; D006352:Heart Ventricles / Q000201:enzymology* / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D008995:Monoamine Oxidase / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress
chemical_list: D000199:Actins; D015415:Biomarkers; D007527:Isoenzymes; D002374:Catalase; C096127:ALDH2 protein, human; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D008995:Monoamine Oxidase