{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T12:57:10Z","timestamp":1793105830520,"version":"4.5.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>Congestive heart failure (CHF) is a leading cause of morbidity and mortality, and oxidative stress has been implicated in the pathogenesis of cachexia (muscle wasting) and the hallmark symptom, exercise intolerance. We have previously shown that a nitric oxide\u2013dependent antioxidant defense renders oxidative skeletal muscle resistant to catabolic wasting. Here, we aimed to identify and determine the functional role of nitric oxide\u2013inducible antioxidant enzyme(s) in protection against cardiac cachexia and exercise intolerance in CHF.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              We demonstrated that systemic administration of endogenous nitric oxide donor\n              <jats:italic>S<\/jats:italic>\n              -nitrosoglutathione in mice blocked the reduction of extracellular superoxide dismutase (EcSOD) protein expression, as well as the induction of\n              <jats:italic>MAFbx\/Atrogin-1<\/jats:italic>\n              mRNA expression and muscle atrophy induced by glucocorticoid. We further showed that endogenous EcSOD, expressed primarily by type IId\/x and IIa myofibers and enriched at endothelial cells, is induced by exercise training. Muscle-specific overexpression of EcSOD by somatic gene transfer or transgenesis (muscle creatine kinase [MCK]-EcSOD) in mice significantly attenuated muscle atrophy. Importantly, when crossbred into a mouse genetic model of CHF (\u03b1-myosin heavy chain\u2013calsequestrin),\n              <jats:italic>MCK-EcSOD<\/jats:italic>\n              transgenic mice had significant attenuation of cachexia with preserved whole body muscle strength and endurance capacity in the absence of reduced HF. Enhanced EcSOD expression significantly ameliorated CHF-induced oxidative stress,\n              <jats:italic>MAFbx\/Atrogin-1<\/jats:italic>\n              mRNA expression, loss of mitochondria, and vascular rarefaction in skeletal muscle.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>EcSOD plays an important antioxidant defense function in skeletal muscle against cardiac cachexia and exercise intolerance in CHF.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circheartfailure.113.000841","type":"journal-article","created":{"date-parts":[[2014,2,13]],"date-time":"2014-02-13T07:09:36Z","timestamp":1392275376000},"page":"519-530","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":70,"title":["Extracellular Superoxide Dismutase Ameliorates Skeletal Muscle Abnormalities, Cachexia, and Exercise Intolerance in Mice with Congestive Heart Failure"],"prefix":"10.1161","volume":"7","author":[{"given":"Mitsuharu","family":"Okutsu","sequence":"first","affiliation":[{"name":"From the Departments of Medicine (M.O., J.A.C., V.A.L., M.Z., J.A.D., C.M.R., B.H.A., Z.Y.), Pharmacology (Z.Y.), and Molecular Physiology and Biological Physics (Z.Y.), Center for Skeletal Muscle Research (M.O., J.A.C., V.A.L., M.Z., J.A.D., Z.Y.), Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA; and Department of Biomedical Engineering, University of Virginia, Charlottesville, VA (B.A.F., K.S.M., S.M.P.-C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jarrod A.","family":"Call","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (M.O., J.A.C., V.A.L., M.Z., J.A.D., C.M.R., B.H.A., Z.Y.), Pharmacology (Z.Y.), and Molecular Physiology and Biological Physics (Z.Y.), Center for Skeletal Muscle Research (M.O., J.A.C., V.A.L., M.Z., J.A.D., Z.Y.), Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA; and Department of Biomedical Engineering, University of Virginia, Charlottesville, VA (B.A.F., K.S.M., S.M.P.-C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitor A.","family":"Lira","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (M.O., J.A.C., V.A.L., M.Z., J.A.D., C.M.R., B.H.A., Z.Y.), Pharmacology (Z.Y.), and Molecular Physiology and Biological Physics (Z.Y.), Center for Skeletal Muscle Research (M.O., J.A.C., V.A.L., M.Z., J.A.D., Z.Y.), Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA; and Department of Biomedical Engineering, University of Virginia, Charlottesville, VA (B.A.F., K.S.M., S.M.P.-C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Zhang","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (M.O., J.A.C., V.A.L., M.Z., J.A.D., C.M.R., B.H.A., Z.Y.), Pharmacology (Z.Y.), and Molecular Physiology and Biological Physics (Z.Y.), Center for Skeletal Muscle Research (M.O., J.A.C., V.A.L., M.Z., J.A.D., Z.Y.), Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA; and Department of Biomedical Engineering, University of Virginia, Charlottesville, VA (B.A.F., K.S.M., S.M.P.-C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean A.","family":"Donet","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (M.O., J.A.C., V.A.L., M.Z., J.A.D., C.M.R., B.H.A., Z.Y.), Pharmacology (Z.Y.), and Molecular Physiology and Biological Physics (Z.Y.), Center for Skeletal Muscle Research (M.O., J.A.C., V.A.L., M.Z., J.A.D., Z.Y.), Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA; and Department of Biomedical Engineering, University of Virginia, Charlottesville, VA (B.A.F., K.S.M., S.M.P.-C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brent A.","family":"French","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (M.O., J.A.C., V.A.L., M.Z., J.A.D., C.M.R., B.H.A., Z.Y.), Pharmacology (Z.Y.), and Molecular Physiology and Biological Physics (Z.Y.), Center for Skeletal Muscle Research (M.O., J.A.C., V.A.L., M.Z., J.A.D., Z.Y.), Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA; and Department of Biomedical Engineering, University of Virginia, Charlottesville, VA (B.A.F., K.S.M., S.M.P.-C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle S.","family":"Martin","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (M.O., J.A.C., V.A.L., M.Z., J.A.D., C.M.R., B.H.A., Z.Y.), Pharmacology (Z.Y.), and Molecular Physiology and Biological Physics (Z.Y.), Center for Skeletal Muscle Research (M.O., J.A.C., V.A.L., M.Z., J.A.D., Z.Y.), Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA; and Department of Biomedical Engineering, University of Virginia, Charlottesville, VA (B.A.F., K.S.M., S.M.P.-C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shayn M.","family":"Peirce-Cottler","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (M.O., J.A.C., V.A.L., M.Z., J.A.D., C.M.R., B.H.A., Z.Y.), Pharmacology (Z.Y.), and Molecular Physiology and Biological Physics (Z.Y.), Center for Skeletal Muscle Research (M.O., J.A.C., V.A.L., M.Z., J.A.D., Z.Y.), Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA; and Department of Biomedical Engineering, University of Virginia, Charlottesville, VA (B.A.F., K.S.M., S.M.P.-C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M.","family":"Rembold","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (M.O., J.A.C., V.A.L., M.Z., J.A.D., C.M.R., B.H.A., Z.Y.), Pharmacology (Z.Y.), and Molecular Physiology and Biological Physics (Z.Y.), Center for Skeletal Muscle Research (M.O., J.A.C., V.A.L., M.Z., J.A.D., Z.Y.), Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA; and Department of Biomedical Engineering, University of Virginia, Charlottesville, VA (B.A.F., K.S.M., S.M.P.-C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian H.","family":"Annex","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (M.O., J.A.C., V.A.L., M.Z., J.A.D., C.M.R., B.H.A., Z.Y.), Pharmacology (Z.Y.), and Molecular Physiology and Biological Physics (Z.Y.), Center for Skeletal Muscle Research (M.O., J.A.C., V.A.L., M.Z., J.A.D., Z.Y.), Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA; and Department of Biomedical Engineering, University of Virginia, Charlottesville, VA (B.A.F., K.S.M., S.M.P.-C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Yan","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (M.O., J.A.C., V.A.L., M.Z., J.A.D., C.M.R., B.H.A., Z.Y.), Pharmacology (Z.Y.), and Molecular Physiology and Biological Physics (Z.Y.), Center for Skeletal Muscle Research (M.O., J.A.C., V.A.L., M.Z., J.A.D., Z.Y.), Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA; and Department of Biomedical Engineering, University of Virginia, Charlottesville, VA (B.A.F., K.S.M., S.M.P.-C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005768-199707000-00004"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/1071-9164(95)90001-2"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.060505"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2010.203356"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/MCO.0b013e328352b4c2"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2011.01.005"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-002-0406-7"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-05-0538"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.atv.0000234921.88489.5c"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200804-549OC"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00851.2003"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/hypertensionaha.107.098186"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.14.6264"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1007625107"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/jgm.1576"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002086"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00481.2009"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1097\/00075197-199905000-00002"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.7.4545"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI1362"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00248.2004"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00192.2009"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M209879200"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007934"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/mus.880130603"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.20487"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1080\/10739680701708436"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2006.01.036"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2008.09.002"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00402.2006"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI9551"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00646.2007"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-005-2755-4"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2010.06.025"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00666-09"},{"key":"e_1_3_4_37_2","first-page":"911","article-title":"Reactive oxygen species-induced apoptosis and necrosis in bovine corneal endothelial cells.","volume":"40","author":"Cho KS","year":"1999","unstructured":"Cho KS, Lee EH, Choi JS, Joo CK. 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