{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T04:15:22Z","timestamp":1790050522995,"version":"4.0.1"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Transl Med"],"published-print":{"date-parts":[[2011,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Duchenne muscular dystrophy (DMD) is an inherited and progressive disease causing striated muscle deterioration. Patients in their twenties generally die from either respiratory or cardiac failure. In order to improve the lifespan and quality of life of DMD patients, it is important to prevent or reverse the progressive loss of contractile function of the heart. Recent studies by our labs have shown that the peptide NBD (Nemo Binding Domain), targeted at blunting Nuclear Factor \u03baB (NF-\u03baB) signaling, reduces inflammation, enhances myofiber regeneration, and improves contractile deficits in the diaphragm in dystrophin-deficient <jats:italic>mdx<\/jats:italic> mice.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>To assess whether cardiac function in addition to diaphragm function can be improved, we investigated physiological and histological parameters of cardiac muscle in mice deficient for both dystrophin and its homolog utrophin (double knockout = dko) mice treated with NBD peptide. These dko mice show classic pathophysiological hallmarks of heart failure, including myocyte degeneration, an impaired force-frequency response and a severely blunted \u03b2-adrenergic response. Cardiac contractile function at baseline and frequencies and pre-loads throughout the in vivo range as well as \u03b2-adrenergic reserve was measured in isolated cardiac muscle preparations. In addition, we studied histopathological and inflammatory markers in these mice.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>At baseline conditions, active force development in cardiac muscles from NBD treated dko mice was more than double that of vehicle-treated dko mice. NBD treatment also significantly improved frequency-dependent behavior of the muscles. The increase in force in NBD-treated dko muscles to \u03b2-adrenergic stimulation was robustly restored compared to vehicle-treated mice. However, histological features, including collagen content and inflammatory markers were not significantly different between NBD-treated and vehicle-treated dko mice.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>We conclude that NBD can significantly improve cardiac contractile dysfunction in the dko mouse model of DMD and may thus provide a novel therapeutic treatment for heart failure.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1479-5876-9-68","type":"journal-article","created":{"date-parts":[[2011,6,17]],"date-time":"2011-06-17T14:58:34Z","timestamp":1308322714000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Improvement of cardiac contractile function by peptide-based inhibition of NF-\u03baB in the utrophin\/dystrophin-deficient murine model of muscular dystrophy"],"prefix":"10.1186","volume":"9","author":[{"given":"Dawn A","family":"Delf\u00edn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer M","family":"Peterson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis C","family":"Guttridge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill A","family":"Rafael-Fortney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul ML","family":"Janssen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2011,5,17]]},"reference":[{"key":"733_CR1","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1152\/physrev.00028.2001","volume":"82","author":"DJ Blake","year":"2002","unstructured":"Blake DJ, Weir A, Newey SE, Davies KE: Function and genetics of dystrophin and dystrophin-related proteins in muscle. Physiol Rev. 2002, 82: 291-329.","journal-title":"Physiol Rev"},{"key":"733_CR2","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1146\/annurev.med.58.011706.144703","volume":"58","author":"EM McNally","year":"2007","unstructured":"McNally EM: New approaches in the therapy of cardiomyopathy in muscular dystrophy. Annual Review of Medicine. 2007, 58: 75-88. 10.1146\/annurev.med.58.011706.144703.","journal-title":"Annual Review of Medicine"},{"issue":"Spec No 2","key":"733_CR3","doi-asserted-by":"publisher","first-page":"R253","DOI":"10.1093\/hmg\/ddl180","volume":"15","author":"D Duan","year":"2006","unstructured":"Duan D: Challenges and opportunities in dystrophin-deficient cardiomyopathy gene therapy. Hum Mol Genet. 2006, 15 (Spec No 2): R253-261.","journal-title":"Hum Mol Genet"},{"key":"733_CR4","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1038\/mt.2008.52","volume":"16","author":"D Townsend","year":"2008","unstructured":"Townsend D, Yasuda S, Li S, Chamberlain JS, Metzger JM: Emergent dilated cardiomyopathy caused by targeted repair of dystrophic skeletal muscle. Mol Ther. 2008, 16: 832-835. 10.1038\/mt.2008.52.","journal-title":"Mol Ther"},{"key":"733_CR5","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1172\/JCI30556","volume":"117","author":"S Acharyya","year":"2007","unstructured":"Acharyya S, Villalta SA, Bakkar N, Bupha-Intr T, Janssen PML, Carathers M, Li ZW, Beg AA, Ghosh S, Sahenk Z, Weinstein M, Gardner KL, Rafael-Fortney JA, Karin M, Tidball JG, Baldwin AS, Guttridge DC: Interplay of IKK\/NF-kappaB signaling in macrophages and myofibers promotes muscle degeneration in Duchenne muscular dystrophy. J Clin Invest. 2007, 117: 889-901. 10.1172\/JCI30556.","journal-title":"J Clin Invest"},{"key":"733_CR6","volume-title":"Molecular Medicine","author":"JM Peterson","year":"2011","unstructured":"Peterson JM, Kline W, Canan BD, Ricca DJ, Kaspar BK, Delf\u00edn DA, DiRienzo K, Clemens PR, Robbins PD, Baldwin AS, Flood P, Kaumaya P, Freitas M, Kornegay JN, Mendell JR, Rafael-Fortney JA, Guttridge DC, Janssen PML: Peptide-based inhibition of NF-\u03baB rescues diaphragm muscle contractile dysfunction in a murine model of Duchenne muscular dystrophy. Molecular Medicine. 2011,"},{"key":"733_CR7","doi-asserted-by":"publisher","first-page":"e11220","DOI":"10.1371\/journal.pone.0011220","volume":"5","author":"AD Guerron","year":"2010","unstructured":"Guerron AD, Rawat R, Sali A, Spurney CF, Pistilli E, Cha HJ, Pandey GS, Gernapudi R, Francia D, Farajian V, Escolar DM, Bossi L, Becker M, Zerr P, de la Porte S, Gordish-Dressman H, Partridge T, Hoffman EP, Nagaraju K: Functional and molecular effects of arginine butyrate and prednisone on muscle and heart in the mdx mouse model of Duchenne Muscular Dystrophy. PLoS One. 2010, 5: e11220-10.1371\/journal.pone.0011220.","journal-title":"PLoS One"},{"key":"733_CR8","doi-asserted-by":"publisher","first-page":"1849","DOI":"10.1016\/S0140-6736(09)61834-1","volume":"374","author":"K Bushby","year":"2009","unstructured":"Bushby K, Lochmuller H, Lynn S, Straub V: Interventions for muscular dystrophy: molecular medicines entering the clinic. Lancet. 2009, 374: 1849-1856. 10.1016\/S0140-6736(09)61834-1.","journal-title":"Lancet"},{"key":"733_CR9","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1016\/S0092-8674(00)80532-2","volume":"90","author":"AE Deconinck","year":"1997","unstructured":"Deconinck AE, Rafael JA, Skinner JA, Brown SC, Potter AC, Metzinger L, Watt DJ, Dickson JG, Tinsley JM, Davies KE: Utrophin-dystrophin-deficient mice as a model for Duchenne muscular dystrophy. Cell. 1997, 90: 717-727. 10.1016\/S0092-8674(00)80532-2.","journal-title":"Cell"},{"key":"733_CR10","doi-asserted-by":"publisher","first-page":"H2373","DOI":"10.1152\/ajpheart.00448.2005","volume":"289","author":"PML Janssen","year":"2005","unstructured":"Janssen PML, Hiranandani N, Mays TA, Rafael-Fortney JA: Utrophin deficiency worsens cardiac contractile dysfunction present in dystrophin-deficient mdx mice. Am J Physiol Heart Circ Physiol. 2005, 289: H2373-2378. 10.1152\/ajpheart.00448.2005.","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"733_CR11","doi-asserted-by":"publisher","first-page":"1743","DOI":"10.1161\/01.CIR.85.5.1743","volume":"85","author":"LA Mulieri","year":"1992","unstructured":"Mulieri LA, Hasenfuss G, Leavitt B, Allen PD, Alpert NR: Altered myocardial force-frequency relation in human heart failure. Circulation. 1992, 85: 1743-1750.","journal-title":"Circulation"},{"key":"733_CR12","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1056\/NEJM198207223070401","volume":"307","author":"MR Bristow","year":"1982","unstructured":"Bristow MR, Ginsburg R, Minobe W, Cubicciotti RS, Sageman WS, Lurie K, Billingham ME, Harrison DC, Stinson EB: Decreased catecholamine sensitivity and beta-adrenergic-receptor density in failing human hearts. N Engl J Med. 1982, 307: 205-211. 10.1056\/NEJM198207223070401.","journal-title":"N Engl J Med"},{"key":"733_CR13","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1016\/S0960-8966(02)00286-9","volume":"13","author":"TA Hainsey","year":"2003","unstructured":"Hainsey TA, Senapati S, Kuhn DE, Rafael JA: Cardiomyopathic features associated with muscular dystrophy are independent of dystrophin absence in cardiovasculature. Neuromuscul Disord. 2003, 13: 294-302. 10.1016\/S0960-8966(02)00286-9.","journal-title":"Neuromuscul Disord"},{"key":"733_CR14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000068446","volume":"99","author":"J Finsterer","year":"2003","unstructured":"Finsterer J, Stollberger C: The heart in human dystrophinopathies. Cardiology. 2003, 99: 1-19. 10.1159\/000068446.","journal-title":"Cardiology"},{"key":"733_CR15","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/j.pharmthera.2009.05.002","volume":"123","author":"KE Porter","year":"2009","unstructured":"Porter KE, Turner NA: Cardiac fibroblasts: at the heart of myocardial remodeling. Pharmacology and Therapeutics. 2009, 123: 255-278. 10.1016\/j.pharmthera.2009.05.002.","journal-title":"Pharmacology and Therapeutics"},{"key":"733_CR16","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.carpath.2005.01.005","volume":"14","author":"PW Fedak","year":"2005","unstructured":"Fedak PW, Verma S, Weisel RD, Li RK: Cardiac remodeling and failure From molecules to man (Part II). Cardiovasc Pathol. 2005, 14: 49-60. 10.1016\/j.carpath.2005.01.005.","journal-title":"Cardiovasc Pathol"},{"key":"733_CR17","doi-asserted-by":"publisher","first-page":"1550","DOI":"10.1126\/science.289.5484.1550","volume":"289","author":"MJ May","year":"2000","unstructured":"May MJ, D'Acquisto F, Madge LA, Glockner J, Pober JS, Ghosh S: Selective inhibition of NF-kappaB activation by a peptide that blocks the interaction of NEMO with the IkappaB kinase complex. Science. 2000, 289: 1550-1554. 10.1126\/science.289.5484.1550.","journal-title":"Science"},{"key":"733_CR18","doi-asserted-by":"publisher","first-page":"5785","DOI":"10.1128\/MCB.19.8.5785","volume":"19","author":"DC Guttridge","year":"1999","unstructured":"Guttridge DC, Albanese C, Reuther JY, Pestell RG, Baldwin AS: NF-kappaB controls cell growth and differentiation through transcriptional regulation of cyclin D1. Mol Cell Biol. 1999, 19: 5785-5799.","journal-title":"Mol Cell Biol"},{"key":"733_CR19","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1006\/jmcc.2002.2065","volume":"34","author":"LB Stull","year":"2002","unstructured":"Stull LB, Leppo M, Marban E, Janssen PML: Physiological determinants of contractile force generation and calcium handling in mouse myocardium. J Mol Cell Cardiol. 2002, 34: 1367-1376. 10.1006\/jmcc.2002.2065.","journal-title":"J Mol Cell Cardiol"},{"issue":"4","key":"733_CR20","doi-asserted-by":"publisher","first-page":"H1092","DOI":"10.1152\/ajpheart.00417.2010","volume":"299","author":"PML Janssen","year":"2010","unstructured":"Janssen PML: Kinetics of Cardiac Muscle Contraction and Relaxation are Linked and Determined by Properties of the Cardiac Sarcomere. Am J Physiol Heart Circ Physiol. 2010, 299 (4): H1092-9. 10.1152\/ajpheart.00417.2010.","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"733_CR21","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1161\/01.RES.46.5.703","volume":"46","author":"HE ter Keurs","year":"1980","unstructured":"ter Keurs HE, Rijnsburger WH, van Heuningen R, Nagelsmit MJ: Tension development and sarcomere length in rat cardiac trabeculae. Evidence of length-dependent activation. Circ Res. 1980, 46: 703-714.","journal-title":"Circ Res"},{"issue":"6","key":"733_CR22","doi-asserted-by":"publisher","first-page":"H1741","DOI":"10.1152\/ajpheart.00759.2010","volume":"299","author":"PML Janssen","year":"2010","unstructured":"Janssen PML: 54th Bowditch Lecture: Myocardial Contraction-Relaxation Coupling. Am J Physiol Heart Circ Physiol. 2010, 299 (6): H1741-9. 10.1152\/ajpheart.00759.2010.","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"733_CR23","doi-asserted-by":"crossref","first-page":"H676","DOI":"10.1152\/ajpheart.1995.269.2.H676","volume":"269","author":"PML Janssen","year":"1995","unstructured":"Janssen PML, Hunter WC: Force, not sarcomere length, correlates with prolongation of isosarcometric contraction. Am J Physiol Heart Circ Physiol. 1995, 269: H676-685.","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"733_CR24","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1016\/j.yjmcc.2007.08.012","volume":"43","author":"PML Janssen","year":"2007","unstructured":"Janssen PML, Periasamy M: Determinants of frequency-dependent contraction and relaxation of mammalian myocardium. J Mol Cell Cardiol. 2007, 43: 523-531. 10.1016\/j.yjmcc.2007.08.012.","journal-title":"J Mol Cell Cardiol"},{"key":"733_CR25","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.yjmcc.2003.09.001","volume":"36","author":"EI Rossman","year":"2004","unstructured":"Rossman EI, Petre RE, Chaudhary KW, Piacentino V, Janssen PML, Gaughan JP, Houser SR, Margulies KB: Abnormal frequency-dependent responses represent the pathophysiologic signature of contractile failure in human myocardium. J Mol Cell Cardiol. 2004, 36: 33-42. 10.1016\/j.yjmcc.2003.09.001.","journal-title":"J Mol Cell Cardiol"},{"key":"733_CR26","doi-asserted-by":"crossref","first-page":"H73","DOI":"10.1152\/ajpheart.1996.271.1.H73","volume":"271","author":"PP de Tombe","year":"1996","unstructured":"de Tombe PP, Wannenburg T, Fan D, Little WC: Right ventricular contractile protein function in rats with left ventricular myocardial infarction. Am J Physiol Heart Circ Physiol. 1996, 271: H73-79.","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"733_CR27","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1111\/j.1469-7793.2001.00535.x","volume":"534","author":"D Georgakopoulos","year":"2001","unstructured":"Georgakopoulos D, Kass D: Minimal force-frequency modulation of inotropy and relaxation of in situ murine heart. J Physiol. 2001, 534: 535-545. 10.1111\/j.1469-7793.2001.00535.x.","journal-title":"J Physiol"},{"key":"733_CR28","doi-asserted-by":"publisher","first-page":"1518","DOI":"10.1053\/j.gastro.2005.07.058","volume":"129","author":"XZ Shi","year":"2005","unstructured":"Shi XZ, Pazdrak K, Saada N, Dai B, Palade P, Sarna SK: Negative transcriptional regulation of human colonic smooth muscle Cav1.2 channels by p50 and p65 subunits of nuclear factor-kappaB. Gastroenterology. 2005, 129: 1518-1532. 10.1053\/j.gastro.2005.07.058.","journal-title":"Gastroenterology"},{"key":"733_CR29","doi-asserted-by":"publisher","first-page":"4094","DOI":"10.1210\/en.2009-0029","volume":"150","author":"MF Tonnesen","year":"2009","unstructured":"Tonnesen MF, Grunnet LG, Friberg J, Cardozo AK, Billestrup N, Eizirik DL, Storling J, Mandrup-Poulsen T: Inhibition of nuclear factor-kappaB or Bax prevents endoplasmic reticulum stress- but not nitric oxide-mediated apoptosis in INS-1E cells. Endocrinology. 2009, 150: 4094-4103. 10.1210\/en.2009-0029.","journal-title":"Endocrinology"},{"key":"733_CR30","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1152\/japplphysiol.00816.2009","volume":"108","author":"E Lima-Cabello","year":"2010","unstructured":"Lima-Cabello E, Cuevas MJ, Garatachea N, Baldini M, Almar M, Gonzalez-Gallego J: Eccentric exercise induces nitric oxide synthase expression through nuclear factor-kappaB modulation in rat skeletal muscle. J Appl Physiol. 2010, 108: 575-583. 10.1152\/japplphysiol.00816.2009.","journal-title":"J Appl Physiol"},{"key":"733_CR31","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1161\/CIRCRESAHA.110.229112","volume":"108","author":"BK Panama","year":"2011","unstructured":"Panama BK, Latour-Villamil D, Farman GP, Zhao D, Bolz SS, Kirshenbaum LA, Backx PH: Nuclear Factor kappaB Downregulates the Transient Outward Potassium Current I(to,f) Through Control of KChIP2 Expression. Circ Res. 2011, 108: 537-543. 10.1161\/CIRCRESAHA.110.229112.","journal-title":"Circ Res"},{"key":"733_CR32","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.2353\/ajpath.2008.071042","volume":"172","author":"D Li","year":"2008","unstructured":"Li D, Yue Y, Duan D: Preservation of muscle force in Mdx3cv mice correlates with low-level expression of a near full-length dystrophin protein. Am J Pathol. 2008, 172: 1332-1341. 10.2353\/ajpath.2008.071042.","journal-title":"Am J Pathol"},{"key":"733_CR33","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1089\/hum.2008.058","volume":"19","author":"B Bostick","year":"2008","unstructured":"Bostick B, Yue Y, Lai Y, Long C, Li D, Duan D: Adeno-associated virus serotype-9 microdystrophin gene therapy ameliorates electrocardiographic abnormalities in mdx mice. Hum Gene Ther. 2008, 19: 851-856. 10.1089\/hum.2008.058.","journal-title":"Hum Gene Ther"},{"key":"733_CR34","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1038\/mt.2008.264","volume":"17","author":"B Bostick","year":"2009","unstructured":"Bostick B, Yue Y, Long C, Marschalk N, Fine DM, Chen J, Duan D: Cardiac expression of a mini-dystrophin that normalizes skeletal muscle force only partially restores heart function in aged Mdx mice. Mol Ther. 2009, 17: 253-261. 10.1038\/mt.2008.264.","journal-title":"Mol Ther"}],"container-title":["Journal of Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1479-5876-9-68.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T14:20:06Z","timestamp":1630506006000},"score":1,"resource":{"primary":{"URL":"https:\/\/translational-medicine.biomedcentral.com\/articles\/10.1186\/1479-5876-9-68"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,5,17]]},"references-count":34,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2011,12]]}},"alternative-id":["733"],"URL":"https:\/\/doi.org\/10.1186\/1479-5876-9-68","relation":{},"ISSN":["1479-5876"],"issn-type":[{"value":"1479-5876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,5,17]]},"assertion":[{"value":"3 February 2011","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 May 2011","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 May 2011","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"68"}}