{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:18:25Z","timestamp":1791415105664,"version":"4.3.3"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2010,1,8]]},"abstract":"<jats:p><jats:bold><jats:italic><jats:underline>Rationale<\/jats:underline>:<\/jats:italic><\/jats:bold>Monoamine oxidases (MAOs) are mitochondrial enzymes that catabolize prohypertrophic neurotransmitters, such as norepinephrine and serotonin, generating hydrogen peroxide. Because excess reactive oxygen species and catecholamines are major contributors to the pathophysiology of congestive heart failure, MAOs could play an important role in this process.<\/jats:p><jats:p><jats:bold><jats:italic><jats:underline>Objective<\/jats:underline>:<\/jats:italic><\/jats:bold>Here, we investigated the role of MAO-A in maladaptive hypertrophy and heart failure.<\/jats:p><jats:p><jats:bold><jats:italic><jats:underline>Methods and Results<\/jats:underline>:<\/jats:italic><\/jats:bold>We report that MAO-A activity is triggered in isolated neonatal and adult myocytes on stimulation with norepinephrine, followed by increase in cell size, reactive oxygen species production, and signs of maladaptive hypertrophy. All of these in vitro changes occur, in part, independently from \u03b1- and \u03b2-adrenergic receptor\u2013operated signaling and are inhibited by the specific MAO-A inhibitor clorgyline. In mice with left ventricular dilation and pump failure attributable to pressure overload, norepinephrine catabolism by MAO-A is increased accompanied by exacerbated oxidative stress. MAO-A inhibition prevents these changes, and also reverses fetal gene reprogramming, metalloproteinase and caspase-3 activation, as well as myocardial apoptosis. The specific role of MAO-A was further tested in mice expressing a dominant-negative MAO-A (MAO-A<jats:sup>neo<\/jats:sup>), which were more protected against pressure overload than their wild-type littermates.<\/jats:p><jats:p><jats:bold><jats:italic><jats:underline>Conclusions<\/jats:underline>:<\/jats:italic><\/jats:bold>In addition to adrenergic receptor\u2013dependent mechanisms, enhanced MAO-A activity coupled with increased intramyocardial norepinephrine availability results in augmented reactive oxygen species generation, contributing to maladaptive remodeling and left ventricular dysfunction in hearts subjected to chronic stress.<\/jats:p>","DOI":"10.1161\/circresaha.109.198366","type":"journal-article","created":{"date-parts":[[2009,11,13]],"date-time":"2009-11-13T03:20:46Z","timestamp":1258082446000},"page":"193-202","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":205,"title":["Monoamine Oxidase A\u2013Mediated Enhanced Catabolism of Norepinephrine Contributes to Adverse Remodeling and Pump Failure in Hearts With Pressure Overload"],"prefix":"10.1161","volume":"106","author":[{"given":"Nina","family":"Kaludercic","sequence":"first","affiliation":[{"name":"From the Division of Cardiology (N.K., E.T., T.N., N.F., D.A.K., N.P.) and Department of Comparative Pathobiology (D.B., K.L.G.), Johns Hopkins Medical Institutions, Baltimore, Md; Department of Biomedical Sciences (N.K., F.D.L.), University of Padova, Italy; Section on Medical Neuroendocrinology (E.W.L., K.P.), National Institute of Child Health and Development, NIH, Bethesda, Md; Department of Pharmacology and Pharmaceutical Sciences (K.C., J.C.S.); and Department of Cell and Neurobiology (J.C.S.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiki","family":"Takimoto","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology (N.K., E.T., T.N., N.F., D.A.K., N.P.) and Department of Comparative Pathobiology (D.B., K.L.G.), Johns Hopkins Medical Institutions, Baltimore, Md; Department of Biomedical Sciences (N.K., F.D.L.), University of Padova, Italy; Section on Medical Neuroendocrinology (E.W.L., K.P.), National Institute of Child Health and Development, NIH, Bethesda, Md; Department of Pharmacology and Pharmaceutical Sciences (K.C., J.C.S.); and Department of Cell and Neurobiology (J.C.S.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Nagayama","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology (N.K., E.T., T.N., N.F., D.A.K., N.P.) and Department of Comparative Pathobiology (D.B., K.L.G.), Johns Hopkins Medical Institutions, Baltimore, Md; Department of Biomedical Sciences (N.K., F.D.L.), University of Padova, Italy; Section on Medical Neuroendocrinology (E.W.L., K.P.), National Institute of Child Health and Development, NIH, Bethesda, Md; Department of Pharmacology and Pharmaceutical Sciences (K.C., J.C.S.); and Department of Cell and Neurobiology (J.C.S.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Feng","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology (N.K., E.T., T.N., N.F., D.A.K., N.P.) and Department of Comparative Pathobiology (D.B., K.L.G.), Johns Hopkins Medical Institutions, Baltimore, Md; Department of Biomedical Sciences (N.K., F.D.L.), University of Padova, Italy; Section on Medical Neuroendocrinology (E.W.L., K.P.), National Institute of Child Health and Development, NIH, Bethesda, Md; Department of Pharmacology and Pharmaceutical Sciences (K.C., J.C.S.); and Department of Cell and Neurobiology (J.C.S.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin W.","family":"Lai","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology (N.K., E.T., T.N., N.F., D.A.K., N.P.) and Department of Comparative Pathobiology (D.B., K.L.G.), Johns Hopkins Medical Institutions, Baltimore, Md; Department of Biomedical Sciences (N.K., F.D.L.), University of Padova, Italy; Section on Medical Neuroendocrinology (E.W.L., K.P.), National Institute of Child Health and Development, NIH, Bethesda, Md; Department of Pharmacology and Pharmaceutical Sciences (K.C., J.C.S.); and Department of Cell and Neurobiology (J.C.S.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Djahida","family":"Bedja","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology (N.K., E.T., T.N., N.F., D.A.K., N.P.) and Department of Comparative Pathobiology (D.B., K.L.G.), Johns Hopkins Medical Institutions, Baltimore, Md; Department of Biomedical Sciences (N.K., F.D.L.), University of Padova, Italy; Section on Medical Neuroendocrinology (E.W.L., K.P.), National Institute of Child Health and Development, NIH, Bethesda, Md; Department of Pharmacology and Pharmaceutical Sciences (K.C., J.C.S.); and Department of Cell and Neurobiology (J.C.S.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Chen","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology (N.K., E.T., T.N., N.F., D.A.K., N.P.) and Department of Comparative Pathobiology (D.B., K.L.G.), Johns Hopkins Medical Institutions, Baltimore, Md; Department of Biomedical Sciences (N.K., F.D.L.), University of Padova, Italy; Section on Medical Neuroendocrinology (E.W.L., K.P.), National Institute of Child Health and Development, NIH, Bethesda, Md; Department of Pharmacology and Pharmaceutical Sciences (K.C., J.C.S.); and Department of Cell and Neurobiology (J.C.S.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen L.","family":"Gabrielson","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology (N.K., E.T., T.N., N.F., D.A.K., N.P.) and Department of Comparative Pathobiology (D.B., K.L.G.), Johns Hopkins Medical Institutions, Baltimore, Md; Department of Biomedical Sciences (N.K., F.D.L.), University of Padova, Italy; Section on Medical Neuroendocrinology (E.W.L., K.P.), National Institute of Child Health and Development, NIH, Bethesda, Md; Department of Pharmacology and Pharmaceutical Sciences (K.C., J.C.S.); and Department of Cell and Neurobiology (J.C.S.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randy D.","family":"Blakely","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology (N.K., E.T., T.N., N.F., D.A.K., N.P.) and Department of Comparative Pathobiology (D.B., K.L.G.), Johns Hopkins Medical Institutions, Baltimore, Md; Department of Biomedical Sciences (N.K., F.D.L.), University of Padova, Italy; Section on Medical Neuroendocrinology (E.W.L., K.P.), National Institute of Child Health and Development, NIH, Bethesda, Md; Department of Pharmacology and Pharmaceutical Sciences (K.C., J.C.S.); and Department of Cell and Neurobiology (J.C.S.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean C.","family":"Shih","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology (N.K., E.T., T.N., N.F., D.A.K., N.P.) and Department of Comparative Pathobiology (D.B., K.L.G.), Johns Hopkins Medical Institutions, Baltimore, Md; Department of Biomedical Sciences (N.K., F.D.L.), University of Padova, Italy; Section on Medical Neuroendocrinology (E.W.L., K.P.), National Institute of Child Health and Development, NIH, Bethesda, Md; Department of Pharmacology and Pharmaceutical Sciences (K.C., J.C.S.); and Department of Cell and Neurobiology (J.C.S.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karel","family":"Pacak","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology (N.K., E.T., T.N., N.F., D.A.K., N.P.) and Department of Comparative Pathobiology (D.B., K.L.G.), Johns Hopkins Medical Institutions, Baltimore, Md; Department of Biomedical Sciences (N.K., F.D.L.), University of Padova, Italy; Section on Medical Neuroendocrinology (E.W.L., K.P.), National Institute of Child Health and Development, NIH, Bethesda, Md; Department of Pharmacology and Pharmaceutical Sciences (K.C., J.C.S.); and Department of Cell and Neurobiology (J.C.S.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Kass","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology (N.K., E.T., T.N., N.F., D.A.K., N.P.) and Department of Comparative Pathobiology (D.B., K.L.G.), Johns Hopkins Medical Institutions, Baltimore, Md; Department of Biomedical Sciences (N.K., F.D.L.), University of Padova, Italy; Section on Medical Neuroendocrinology (E.W.L., K.P.), National Institute of Child Health and Development, NIH, Bethesda, Md; Department of Pharmacology and Pharmaceutical Sciences (K.C., J.C.S.); and Department of Cell and Neurobiology (J.C.S.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Di Lisa","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology (N.K., E.T., T.N., N.F., D.A.K., N.P.) and Department of Comparative Pathobiology (D.B., K.L.G.), Johns Hopkins Medical Institutions, Baltimore, Md; Department of Biomedical Sciences (N.K., F.D.L.), University of Padova, Italy; Section on Medical Neuroendocrinology (E.W.L., K.P.), National Institute of Child Health and Development, NIH, Bethesda, Md; Department of Pharmacology and Pharmaceutical Sciences (K.C., J.C.S.); and Department of Cell and Neurobiology (J.C.S.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazareno","family":"Paolocci","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology (N.K., E.T., T.N., N.F., D.A.K., N.P.) and Department of Comparative Pathobiology (D.B., K.L.G.), Johns Hopkins Medical Institutions, Baltimore, Md; Department of Biomedical Sciences (N.K., F.D.L.), University of Padova, Italy; Section on Medical Neuroendocrinology (E.W.L., K.P.), National Institute of Child Health and Development, NIH, Bethesda, Md; Department of Pharmacology and Pharmaceutical Sciences (K.C., J.C.S.); and Department of Cell and Neurobiology (J.C.S.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00012.2007"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1341.019"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4020-6191-2_20"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1071-9164(00)80002-0"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2007.1995"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.0000254415.31362.a7"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.2002.1526"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1527-5299.2002.00717.x"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(96)00140-4"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200524408"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.107.737031"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1883"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004410100361"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.12-05-01977.1992"},{"key":"e_1_3_3_15_2","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/S0022-3565(25)30287-9","volume":"194","year":"1975","unstructured":"Lowe MC, Reichenbach DD, Horita A. 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