{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T04:27:19Z","timestamp":1791606439505,"version":"4.3.4"},"reference-count":200,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2019,8,22]],"date-time":"2019-08-22T00:00:00Z","timestamp":1566432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-HL114832"],"award-info":[{"award-number":["R01-HL114832"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["F31-139093"],"award-info":[{"award-number":["F31-139093"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Duchenne muscular dystrophy (DMD) is a devastating disease featuring skeletal muscle wasting, respiratory insufficiency, and cardiomyopathy. Historically, respiratory failure has been the leading cause of mortality in DMD, but recent improvements in symptomatic respiratory management have extended the life expectancy of DMD patients. With increased longevity, the clinical relevance of heart disease in DMD is growing, as virtually all DMD patients over 18 year of age display signs of cardiomyopathy. This review will focus on the pathophysiological basis of DMD in the heart and discuss the therapeutic approaches currently in use and those in development to treat dystrophic cardiomyopathy. The first section will describe the aspects of the DMD that result in the loss of cardiac tissue and accumulation of fibrosis. The second section will discuss cardiac small molecule therapies currently used to treat heart disease in DMD, with a focus on the evidence supporting the use of each drug in dystrophic patients. The final section will outline the strengths and limitations of approaches directed at correcting the genetic defect through dystrophin gene replacement, modification, or repair. There are several new and promising therapeutic approaches that may protect the dystrophic heart, but their limitations suggest that future management of dystrophic cardiomyopathy may benefit from combining gene-targeted therapies with small molecule therapies. Understanding the mechanistic basis of dystrophic heart disease and the effects of current and emerging therapies will be critical for their success in the treatment of patients with DMD.<\/jats:p>","DOI":"10.3390\/ijms20174098","type":"journal-article","created":{"date-parts":[[2019,8,23]],"date-time":"2019-08-23T10:15:07Z","timestamp":1566555307000},"page":"4098","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":125,"title":["Cardiac Pathophysiology and the Future of Cardiac Therapies in Duchenne Muscular Dystrophy"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9904-9140","authenticated-orcid":false,"given":"Tatyana A.","family":"Meyers","sequence":"first","affiliation":[{"name":"Department of Integrative Biology and Physiology, Medical School, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"DeWayne","family":"Townsend","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and Physiology, Medical School, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1016\/S0960-8966(02)00140-2","article-title":"Survival in Duchenne muscular dystrophy: Improvements in life expectancy since 1967 and the impact of home nocturnal ventilation","volume":"12","author":"Eagle","year":"2002","journal-title":"Neuromuscul. Disord."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1161\/CIRCRESAHA.116.308402","article-title":"Duchenne muscular dystrophy mice and men: Can understanding a genetic cardiomyopathy inform treatment of other myocardial diseases?","volume":"118","author":"Chadwick","year":"2016","journal-title":"Circ. Res."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"3 Nigro, G., Comi, L.I., Politano, L., and Bain, R.J.I. (1990). The incidence and evolution of cardiomyopathy in Duchenne muscular dystrophy. Int. J. Cardiol., 26, 271\u2013277.","DOI":"10.1016\/0167-5273(90)90082-G"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1002\/mus.24163","article-title":"CINRG Duchenne Natural History Study demonstrates insufficient diagnosis and treatment of cardiomyopathy in Duchenne muscular dystrophy","volume":"50","author":"Spurney","year":"2014","journal-title":"Muscle Nerve"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1161\/CIRCULATIONAHA.114.015151","article-title":"Contemporary cardiac issues in Duchenne muscular dystrophy","volume":"131","author":"McNally","year":"2015","journal-title":"Circulation"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/S1474-4422(18)30025-5","article-title":"Diagnosis and management of Duchenne muscular dystrophy, part 2: Respiratory, cardiac, bone health, and orthopaedic management","volume":"17","author":"Birnkrant","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2533","DOI":"10.1016\/j.jacc.2016.02.081","article-title":"Dystrophin-Deficient Cardiomyopathy","volume":"67","author":"Kamdar","year":"2016","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1002\/humu.22758","article-title":"The TREAT-NMD DMD Global Database: Analysis of more than 7,000 Duchenne muscular dystrophy mutations","volume":"36","author":"Bladen","year":"2015","journal-title":"Hum. Mutat."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Flanigan, K.M. (2017). Duchenne and Becker Muscular Dystrophies. Swaiman\u2019s Pediatric Neurology, Elsevier Inc.. [6th ed.].","DOI":"10.1016\/B978-0-323-37101-8.00146-6"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1002\/ana.23528","article-title":"Evidence-Based Path to Newborn Screening for Duchenne Muscular Dystrophy","volume":"71","author":"Mendell","year":"2012","journal-title":"Ann. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.nmd.2014.03.008","article-title":"A systematic review and meta-analysis on the epidemiology of Duchenne and Becker muscular dystrophy","volume":"24","author":"Mah","year":"2014","journal-title":"Neuromuscul. Disord."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1146\/annurev-genom-090314-025003","article-title":"The Pathogenesis and Therapy of Muscular Dystrophies","volume":"16","author":"Guiraud","year":"2015","journal-title":"Annu. Rev. Genomics Hum. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1093\/hmg\/ddu537","article-title":"Becker muscular dystrophy severity is linked to the structure of dystrophin","volume":"24","author":"Nicolas","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1002\/mus.10435","article-title":"Origins and early descriptions of \u201cDuchenne muscular dystrophy\u201d","volume":"28","author":"Tyler","year":"2003","journal-title":"Muscle Nerve"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/s00256-011-1240-1","article-title":"Lower leg muscle involvement in Duchenne muscular dystrophy: An MR imaging and spectroscopy study","volume":"41","author":"Torriani","year":"2012","journal-title":"Skeletal Radiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/S1474-4422(18)30026-7","article-title":"Diagnosis and management of Duchenne muscular dystrophy, part 3: Primary care, emergency management, psychosocial care, and transitions of care across the lifespan","volume":"17","author":"Birnkrant","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1177\/0883073815570154","article-title":"Cognitive and neurobehavioral profile in boys with duchenne muscular dystrophy","volume":"30","author":"Banihani","year":"2015","journal-title":"J. Child Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1161\/JAHA.114.001338","article-title":"Myocardial fibrosis burden predicts left ventricular ejection fraction and is associated with age and steroid treatment duration in Duchenne muscular dystrophy","volume":"4","author":"Tandon","year":"2015","journal-title":"J. Am. Heart Assoc."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1016\/j.jacc.2008.12.032","article-title":"Circumferential Strain Analysis Identifies Strata of Cardiomyopathy in Duchenne Muscular Dystrophy. A Cardiac Magnetic Resonance Tagging Study","volume":"53","author":"Hor","year":"2009","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/j.nmd.2018.06.014","article-title":"Advances in the diagnosis and management of cardiomyopathy in Duchenne muscular dystrophy","volume":"28","author":"Hor","year":"2018","journal-title":"Neuromuscul. Disord."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.braindev.2007.01.009","article-title":"Cardiac troponin I for accurate evaluation of cardiac status in myopathic patients","volume":"29","author":"Matsumura","year":"2007","journal-title":"Brain Dev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1111\/j.1440-1754.2012.02428.x","article-title":"Evaluation of the North Star Ambulatory Assessment scale and cardiac abnormalities in ambulant boys with Duchenne muscular dystrophy","volume":"48","author":"Ergul","year":"2012","journal-title":"J. Paediatr. Child Health"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1007\/s00246-002-0408-9","article-title":"Myocardial cell damage in Duchenne muscular dystrophy","volume":"24","author":"Ramaciotti","year":"2003","journal-title":"Pediatr. Cardiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1161\/JAHA.117.006340","article-title":"Predictors of death in adults with Duchenne muscular dystrophy-associated cardiomyopathy","volume":"6","author":"Cheeran","year":"2017","journal-title":"J. Am. Heart Assoc."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.nmd.2007.03.002","article-title":"Managing Duchenne muscular dystrophy\u2014The additive effect of spinal surgery and home nocturnal ventilation in improving survival","volume":"17","author":"Eagle","year":"2007","journal-title":"Neuromuscul. Disord."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1083\/jcb.150.5.1209","article-title":"The dystrophin complex forms a mechanically strong link between the sarcolemma and costameric actin","volume":"150","author":"Rybakova","year":"2000","journal-title":"J. Cell Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.bbadis.2006.05.010","article-title":"Dystrophin, its interactions with other proteins, and implications for muscular dystrophy","volume":"1772","author":"Ervasti","year":"2007","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1007\/s10974-013-9362-9","article-title":"Alterations of dystrophin-associated glycoproteins in the heart lacking dystrophin or dystrophin and utrophin","volume":"34","author":"Sharpe","year":"2013","journal-title":"J. Muscle Res. Cell Motil."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1038\/sj.mt.6300144","article-title":"Systemic administration of micro-dystrophin restores cardiac geometry and prevents dobutamine-induced cardiac pump failure","volume":"15","author":"Townsend","year":"2007","journal-title":"Mol. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"307","DOI":"10.3233\/JND-170253","article-title":"Progression of Duchenne Cardiomyopathy Presenting with Chest Pain and Troponin Elevation","volume":"4","author":"Hor","year":"2017","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.yjmcc.2019.01.013","article-title":"Acute AT1R blockade prevents isoproterenol-induced injury in mdx hearts","volume":"128","author":"Meyers","year":"2019","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1093\/hmg\/ddh174","article-title":"Full-length dystrophin expression in half of the heart cells ameliorates \u03b2-isoproterenol-induced cardiomyopathy in mdx mice","volume":"13","author":"Yue","year":"2004","journal-title":"Hum. Mol. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5104","DOI":"10.1038\/s41467-018-07639-3","article-title":"Loss of peroxiredoxin-2 exacerbates eccentric contraction-induced force loss in dystrophin-deficient muscle","volume":"9","author":"Olthoff","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1172\/JCI30848","article-title":"Dysferlin-mediated membrane repair protects the heart from stress-induced left ventricular injury","volume":"117","author":"Han","year":"2007","journal-title":"J. Clin. Invest."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/ncb1812","article-title":"MG53 nucleates assembly of cell membrane repair machinery","volume":"11","author":"Cai","year":"2009","journal-title":"Nat. Cell Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.yjmcc.2017.08.007","article-title":"MG53 is dispensable for T-tubule maturation but critical for maintaining T-tubule integrity following cardiac stress","volume":"112","author":"Zhang","year":"2017","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7554\/eLife.17589","article-title":"Thrombospondin expression in myofibers stabilizes muscle membranes","volume":"5","author":"Vanhoutte","year":"2016","journal-title":"Elife"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/MCB.00114-18","article-title":"Defective Flux of Thrombospondin-4 through the Secretory Pathway Impairs Cardiomyocyte Membrane Stability and Causes Cardiomyopathy","volume":"38","author":"Brody","year":"2018","journal-title":"Mol. Cell. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e89","DOI":"10.1212\/NXG.0000000000000089","article-title":"The clinical outcome study for dysferlinopathy: An international multicenter study","volume":"2","author":"Harris","year":"2016","journal-title":"Neurol. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/mt.2012.5","article-title":"Enhancing muscle membrane repair by gene delivery of MG53 ameliorates muscular dystrophy and heart failure in\u03b4-sarcoglycan-deficient hamsters","volume":"20","author":"He","year":"2012","journal-title":"Mol. Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"139ra85","DOI":"10.1126\/scitranslmed.3003921","article-title":"Recombinant MG53 protein modulates therapeutic cell membrane repair in treatment of muscular dystrophy","volume":"4","author":"Weisleder","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"10657","DOI":"10.1021\/acs.jpcb.7b08938","article-title":"All-Atom Molecular Dynamics-Based Analysis of Membrane-Stabilizing Copolymer Interactions with Lipid Bilayers Probed under Constant Surface Tensions","volume":"121","author":"Houang","year":"2017","journal-title":"J. Phys. Chem. B"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13395-018-0177-7","article-title":"Muscle membrane integrity in Duchenne muscular dystrophy: Recent advances in copolymer-based muscle membrane stabilizers","volume":"8","author":"Houang","year":"2018","journal-title":"Skelet. Muscle"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1172\/JCI41329","article-title":"Chronic administration of membrane sealant prevents severe cardiac injury and ventricular dilatation in dystrophic dogs","volume":"120","author":"Townsend","year":"2010","journal-title":"J. Clin. Invest."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1038\/nature03844","article-title":"Dystrophic heart failure blocked by membrane sealant poloxamer","volume":"436","author":"Yasuda","year":"2005","journal-title":"Nature"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"15042","DOI":"10.1038\/mtm.2015.42","article-title":"Membrane-stabilizing copolymers confer marked protection to dystrophic skeletal muscle in vivo","volume":"2","author":"Houang","year":"2015","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1586\/14779072.5.1.99","article-title":"Cardiomyopathy of Duchenne muscular dystrophy: Pathogenesis and prospect of membrane sealants as a new therapeutic approach","volume":"5","author":"Townsend","year":"2007","journal-title":"Expert Rev. Cardiovasc. Ther."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e16","DOI":"10.1017\/erm.2014.17","article-title":"Dysregulation of calcium homeostasis in muscular dystrophies","volume":"16","author":"Aldanondo","year":"2014","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"H846","DOI":"10.1152\/ajpheart.00688.2006","article-title":"Intracellular calcium handling in ventricular myocytes from mdx mice","volume":"292","author":"Williams","year":"2007","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Johnstone, V.P.A., Viola, H.M., and Hool, L.C. (2017). Dystrophic cardiomyopathy\u2014Potential role of calcium in pathogenesis, treatment and novel therapies. Genes (Basel), 8.","DOI":"10.3390\/genes8040108"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.biocel.2010.11.005","article-title":"Duchenne muscular dystrophy\u2014What causes the increased membrane permeability in skeletal muscle?","volume":"43","author":"Allen","year":"2010","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1093\/cvr\/cvv021","article-title":"Dystrophic cardiomyopathy: Role of TRPV2 channels in stretch-induced cell damage","volume":"106","author":"Lorin","year":"2015","journal-title":"Cardiovasc. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1113\/jphysiol.2005.091694","article-title":"Mechanisms of stretch-induced muscle damage in normal and dystrophic muscle: Role of ionic changes","volume":"567","author":"Allen","year":"2005","journal-title":"J. Physiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"H564","DOI":"10.1152\/ajpheart.00441.2013","article-title":"Enhanced currents through L-type calcium channels in cardiomyocytes disturb the electrophysiology of the dystrophic heart","volume":"306","author":"Koenig","year":"2014","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"H767","DOI":"10.1152\/ajpheart.00700.2012","article-title":"L-type Ca2+ channel contributes to alterations in mitochondrial calcium handling in the mdx ventricular myocyte","volume":"304","author":"Viola","year":"2013","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"C1502-11","DOI":"10.1152\/ajpcell.00435.2001","article-title":"Regulation of the cardiac L-type Ca2+ channel by the actin-binding proteins alpha-actinin and dystrophin","volume":"282","author":"Sadeghi","year":"2002","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e151","DOI":"10.1016\/j.ddmec.2010.09.009","article-title":"Fixing ryanodine receptor Ca2+ leak\u2014A novel therapeutic strategy for contractile failure in heart and skeletal muscle","volume":"7","author":"Andersson","year":"2010","journal-title":"Drug Discov. Today Dis. Mech."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1073\/pnas.0908540107","article-title":"Leaky RyR2 trigger ventricular arrhythmias in Duchenne muscular dystrophy","volume":"107","author":"Fauconnier","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/nm.1916","article-title":"Hypernitrosylated ryanodine receptor calcium release channels are leaky in dystrophic muscle","volume":"15","author":"Bellinger","year":"2009","journal-title":"Nat. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"13165","DOI":"10.1073\/pnas.1004509107","article-title":"Genetic inhibition of PKA phosphorylation of RyR2 prevents dystrophic cardiomyopathy","volume":"107","author":"Sarma","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.yjmcc.2015.11.009","article-title":"Crosstalk between RyR2 oxidation and phosphorylation contributes to cardiac dysfunction in mice with Duchenne muscular dystrophy","volume":"89","author":"Wang","year":"2015","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1038\/s41467-017-01146-7","article-title":"Reducing sarcolipin expression mitigates Duchenne muscular dystrophy and associated cardiomyopathy in mice","volume":"8","author":"Voit","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.bbrc.2003.09.005","article-title":"Decreased mAKAP, ryanodine receptor, and SERCA2a gene expression in mdx hearts","volume":"310","author":"Rohman","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2266","DOI":"10.1016\/j.biocel.2013.05.001","article-title":"Wasting mechanisms in muscular dystrophy","volume":"45","author":"Shin","year":"2013","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2413","DOI":"10.1056\/NEJMra043361","article-title":"Calpains and Disease","volume":"352","author":"Zatz","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1093\/cvr\/cvs099","article-title":"The role of calpains in myocardial remodelling and heart failure","volume":"96","author":"Letavernier","year":"2012","journal-title":"Cardiovasc. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0166839","article-title":"Activation of both the calpain and ubiquitin-proteasome systems contributes to septic cardiomyopathy through dystrophin loss\/disruption and mTOR inhibition","volume":"11","author":"Freitas","year":"2016","journal-title":"PLoS ONE"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2959","DOI":"10.1021\/bi2018909","article-title":"Role of mitochondrial Ca2+ in the regulation of cellular energetics","volume":"51","author":"Glancy","year":"2012","journal-title":"Biochemistry"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1016\/j.bbabio.2009.06.009","article-title":"Mitochondrial calcium and the permeability transition in cell death","volume":"1787","author":"Lemasters","year":"2009","journal-title":"Biochim. Biophys. Acta Bioenerg."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.ceca.2015.04.006","article-title":"Mitochondrial dysfunctions during progression of dystrophic cardiomyopathy","volume":"58","author":"Kyrychenko","year":"2015","journal-title":"Cell Calcium"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1038\/nm1736","article-title":"Genetic and pharmacologic inhibition of mitochondrial-dependent necrosis attenuates muscular dystrophy","volume":"14","author":"Millay","year":"2008","journal-title":"Nat. Med."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Ingwall, J.S. (2002). ATP and the Heart, Springer. [1st ed.].","DOI":"10.1007\/978-1-4615-1093-2"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Cui, W., Jang, A., Zhang, P., Thompson, B., Townsend, D., Metzger, J.M., and Zhang, J. (2015). Early detection of myocardial bioenergetic deficits: A 9.4 tesla complete non invasive 31P MR spectroscopy study in mice with muscular dystrophy. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0135000"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1016\/j.yjmcc.2008.09.125","article-title":"Abnormal cardiac morphology, function and energy metabolism in the dystrophic mdx mouse: An MRI and MRS study","volume":"45","author":"Zhang","year":"2008","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"H938","DOI":"10.1152\/ajpheart.00917.2015","article-title":"Hypoxia-induced cardiac injury in dystrophic mice","volume":"310","author":"Stelter","year":"2016","journal-title":"Am. J. Physiol. Hear. Circ. Physiol."},{"key":"ref_76","first-page":"186","article-title":"Deficit in PINK1\/PARKIN-mediated mitochondrial autophagy at late stages of dystrophic cardiomyopathy","volume":"58","author":"Kang","year":"2018","journal-title":"Cardiovasc. Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1016\/S0735-1097(00)00960-8","article-title":"Magnetic resonance spectroscopy evidence of abnormal cardiac energetics in Xp21 muscular dystrophy","volume":"36","author":"Crilley","year":"2000","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"H144","DOI":"10.1152\/ajpheart.00522.2010","article-title":"Stress-induced opening of the permeability transition pore in the dystrophin-deficient heart is attenuated by acute treatment with sildenafil","volume":"300","author":"Ascah","year":"2011","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"H1125","DOI":"10.1152\/ajpheart.00436.2008","article-title":"Transient opening of mitochondrial permeability transition pore by reactive oxygen species protects myocardium from ischemia-reperfusion injury","volume":"296","author":"Saotome","year":"2009","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/S0006-3495(99)77239-5","article-title":"Transient and long-lasting openings of the mitochondrial permeability transition pore can be monitored directly in intact cells by changes in mitochondrial calcein fluorescence","volume":"76","author":"Petronilli","year":"1999","journal-title":"Biophys. J."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.1161\/01.CIR.0000126294.81407.7D","article-title":"Transient Mitochondrial Permeability Transition Pore Opening Mediates Preconditioning-Induced Protection","volume":"109","author":"Hausenloy","year":"2004","journal-title":"Circulation"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"14126","DOI":"10.1073\/pnas.241380298","article-title":"Identification of a neuronal nitric oxide synthase in isolated cardiac mitochondria using electrochemical detection","volume":"98","author":"Kanai","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.yjmcc.2014.08.013","article-title":"Dystrobrevin increases dystrophin\u2019s binding to the dystrophin-glycoprotein complex and provides protection during cardiac stress","volume":"76","author":"Strakova","year":"2014","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1126\/science.1202768","article-title":"X-ROS signaling: Rapid mechano-chemo transduction in heart","volume":"333","author":"Prosser","year":"2011","journal-title":"Science"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"H710","DOI":"10.1152\/ajpheart.00890.2013","article-title":"NADPH oxidase-2 inhibition restores contractility and intracellular calcium handling and reduces arrhythmogenicity in dystrophic cardiomyopathy","volume":"307","author":"Gonzalez","year":"2014","journal-title":"Am. J. Physiol. Hear. Circ. Physiol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7554\/eLife.31732","article-title":"NADPH oxidase mediates microtubule alterations and diaphragm dysfunction in dystrophic mice","volume":"7","author":"Loehr","year":"2018","journal-title":"Elife"},{"key":"ref_87","first-page":"4951","article-title":"Independent variability of microtubule perturbations associated with dystrophinopathy","volume":"25","author":"Belanto","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Matecki, S., Fauconnier, J., and Lacampagne, A. (2014). Reactive Oxygen Species and Muscular Dystrophy. Syst. Biol. Free Radicals Antioxid., 3055\u20133072.","DOI":"10.1007\/978-3-642-30018-9_136"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1089\/ars.2012.4604","article-title":"Angiotensin II-Induced Production of Mitochondrial Reactive Oxygen Species: Potential Mechanisms and Relevance for Cardiovascular Disease","volume":"19","author":"Dikalov","year":"2013","journal-title":"Antioxid. Redox Signal."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1152\/physrev.00007.2015","article-title":"Absence of Dystrophin Disrupts Skeletal Muscle Signaling: Roles of Ca2+, Reactive Oxygen Species, and Nitric Oxide in the Development of Muscular Dystrophy","volume":"96","author":"Allen","year":"2015","journal-title":"Physiol. Rev."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.yjmcc.2012.11.011","article-title":"X-ROS signaling in the heart and skeletal muscle: Stretch-dependent local ROS regulates [Ca2+]i","volume":"58","author":"Prosser","year":"2013","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2555","DOI":"10.1093\/eurheartj\/ehv305","article-title":"Pathophysiological role of oxidative stress in systolic and diastolic heart failure and its therapeutic implications","volume":"36","author":"Gori","year":"2015","journal-title":"Eur. Heart J."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1074\/jbc.M708000200","article-title":"Mechanism of angiotensin II-induced superoxide production in cells reconstituted with angiotensin type 1 receptor and the components of NADPH oxidase","volume":"283","author":"Choi","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1177\/1074248410381757","article-title":"Losartan decreases cardiac muscle fibrosis and improves cardiac function in dystrophin-deficient mdx mice","volume":"16","author":"Spurney","year":"2011","journal-title":"J. Cardiovasc. Pharmacol. Ther."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.lfs.2015.10.023","article-title":"Chronic effects of losartan on the muscles and the serologic profiles of mdx mice","volume":"143","author":"Lee","year":"2015","journal-title":"Life Sci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/0092-8674(95)90471-9","article-title":"Nitric oxide synthase complexed with dystrophin and absent from skeletal muscle sarcolemma in Duchenne muscular dystrophy","volume":"82","author":"Brenman","year":"1995","journal-title":"Cell"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"162ra155","DOI":"10.1126\/scitranslmed.3004327","article-title":"Tadalafil alleviates muscle ischemia in patients with becker muscular dystrophy","volume":"4","author":"Martin","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"15090","DOI":"10.1073\/pnas.95.25.15090","article-title":"Impaired metabolic modulation of alpha-adrenergic vasoconstriction in dystrophin-deficient skeletal muscle","volume":"95","author":"Thomas","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Johnson, E.K., Zhang, L., Adams, M.E., Phillips, A., Freitas, M.A., Froehner, S.C., Green-Church, K.B., and Montanaro, F. (2012). Proteomic analysis reveals new cardiac-specific dystrophin-associated proteins. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0043515"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1006\/jmcc.1999.1018","article-title":"Decreased myocardial nNOS, increased iNOS and abnormal ECGs in mouse models of duchenne muscular dystrophy","volume":"31","author":"Bia","year":"1999","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1042\/BJ20120787","article-title":"Nitric oxide signalling pathway in Duchenne muscular dystrophy mice: Up-regulation of L-arginine transporters","volume":"449","author":"Ramachandran","year":"2012","journal-title":"Biochem. J."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"13663","DOI":"10.1073\/pnas.1512991112","article-title":"Dystrophin\u2013glycoprotein complex regulates muscle nitric oxide production through mechanoregulation of AMPK signaling","volume":"112","author":"Garbincius","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"27580","DOI":"10.1016\/S0021-9258(18)47024-X","article-title":"Cytokine-inducible nitric oxide synthase (iNOS) expression in cardiac myocytes. Characterization and regulation of iNOS expression and detection of iNOS activity in single cardiac myocytes in vitro","volume":"269","author":"Balligand","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"20876","DOI":"10.1074\/jbc.M112.344929","article-title":"Increased resting intracellular calcium modulates NF-\u03baB-dependent inducible nitric-oxide synthase gene expression in dystrophic mdx skeletal myotubes","volume":"287","author":"Altamirano","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1161\/01.RES.0000088351.58510.21","article-title":"Nitric oxide and cardiac function: Ten years after, and continuing","volume":"93","author":"Massion","year":"2003","journal-title":"Circ. Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"19079","DOI":"10.1073\/pnas.1013077107","article-title":"Sildenafil reverses cardiac dysfunction in the mdx mouse model of Duchenne muscular dystrophy","volume":"107","author":"Adamo","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"7028","DOI":"10.1073\/pnas.0710595105","article-title":"Sildenafil and cardiomyocyte-specific cGMP signaling prevent cardiomyopathic changes associated with dystrophin deficiency","volume":"105","author":"Khairallah","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"13818","DOI":"10.1073\/pnas.250379497","article-title":"Functional muscle ischemia in neuronal nitric oxide synthase-deficient skeletal muscle of children with Duchenne muscular dystrophy","volume":"97","author":"Sander","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1002\/ana.24214","article-title":"Sildenafil does not improve cardiomyopathy in Duchenne\/Becker muscular dystrophy","volume":"76","author":"Leung","year":"2014","journal-title":"Ann. Neurol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"E10763","DOI":"10.1073\/pnas.1712623114","article-title":"Transient receptor potential channel 6 regulates abnormal cardiac S-nitrosylation in Duchenne muscular dystrophy","volume":"114","author":"Chung","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"3189","DOI":"10.1093\/hmg\/ddu029","article-title":"Partial restoration of cardiac function with \u0394PDZ nNOS in aged mdx model of Duchenne cardiomyopathy","volume":"23","author":"Lai","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.1093\/hmg\/ddi197","article-title":"Cardiomyopathy in dystrophin-deficient hearts is prevented by expression of a neuronal nitric oxide synthase transgene in the myocardium","volume":"14","author":"Jordan","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Wehling-Henricks, M., and Tidball, J.G. (2011). Neuronal nitric oxide synthase-rescue of dystrophin\/utrophin double knockout mice does not require nNOS localization to the cell membrane. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0025071"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1532-429X-15-107","article-title":"Prevalence and distribution of late gadolinium enhancement in a large population of patients with Duchenne muscular dystrophy: Effect of age and left ventricular systolic function","volume":"15","author":"Hor","year":"2013","journal-title":"J. Cardiovasc. Magn. Reson."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1007\/s00018-013-1349-6","article-title":"The pathogenesis of cardiac fibrosis","volume":"71","author":"Kong","year":"2014","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.pharmthera.2009.05.002","article-title":"Cardiac fibroblasts: At the heart of myocardial remodeling","volume":"123","author":"Porter","year":"2009","journal-title":"Pharmacol. Ther."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.actbio.2019.03.017","article-title":"Cardiomyocytes facing fibrotic conditions re-express extracellular matrix transcripts","volume":"89","author":"Mikhael","year":"2019","journal-title":"Acta Biomater."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.cardfail.2019.02.006","article-title":"The Role of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Duchenne Muscular Dystrophy Cardiomyopathy","volume":"25","author":"Soslow","year":"2019","journal-title":"J. Card. Fail."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.matbio.2018.01.014","article-title":"Regulation of fibrosis in muscular dystrophy","volume":"68\u201369","author":"Smith","year":"2018","journal-title":"Matrix Biol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.trsl.2017.10.001","article-title":"Cardiac macrophage biology in the steady-state heart, the aging heart, and following myocardial infarction","volume":"191","author":"Ma","year":"2018","journal-title":"Transl. Res."},{"key":"ref_121","first-page":"5167","article-title":"Myeloid cells are capable of synthesizing aldosterone to exacerbate damage in muscular dystrophy","volume":"25","author":"Chadwick","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1161\/CIRCULATIONAHA.111.031716","article-title":"Early treatment with lisinopril and spironolactone preserves cardiac and skeletal muscle in Duchenne muscular dystrophy mice","volume":"124","author":"Chimanji","year":"2011","journal-title":"Circulation"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"H293","DOI":"10.1152\/ajpheart.1992.263.1.H293","article-title":"A method to reconstruct myocardial sarcomere lengths and orientations at transmural sites in beating canine hearts","volume":"263","author":"Rodriguez","year":"2017","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.tcm.2017.12.006","article-title":"ACE inhibition to slow progression of myocardial fibrosis in muscular dystrophies","volume":"28","author":"Russo","year":"2018","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"e201800186","DOI":"10.26508\/lsa.201800186","article-title":"Vamorolone targets dual nuclear receptors to treat inflammation and dystrophic cardiomyopathy","volume":"2","author":"Heier","year":"2019","journal-title":"Life Sci. Alliance"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1","DOI":"10.14814\/phy2.14018","article-title":"Simvastatin provides long-term improvement of left ventricular function and prevents cardiac fibrosis in muscular dystrophy","volume":"7","author":"Kim","year":"2019","journal-title":"Physiol. Rep."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.drudis.2010.11.016","article-title":"Angiotensin II receptors and drug discovery in cardiovascular disease","volume":"16","author":"Dasgupta","year":"2011","journal-title":"Drug Discov. Today"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1038\/hr.2009.5","article-title":"Inhibition of the renin\u2013angiotensin system and target organ protection","volume":"32","author":"Iwanami","year":"2009","journal-title":"Hypertens. Res."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.phrs.2017.05.008","article-title":"AT1 receptor signaling pathways in the cardiovascular system","volume":"125","author":"Kawai","year":"2017","journal-title":"Pharmacol. Res."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/j.jacc.2004.09.078","article-title":"Effect of perindopril on the onset and progression of left ventricular dysfunction in Duchenne muscular dystrophy","volume":"45","author":"Duboc","year":"2005","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/j.ahj.2007.05.014","article-title":"Perindopril preventive treatment on mortality in Duchenne muscular dystrophy: 10 years\u2019 follow-up","volume":"154","author":"Duboc","year":"2007","journal-title":"Am. Heart J."},{"key":"ref_132","first-page":"1659","article-title":"A trial of the beta-blocker bucindolol in patients with advanced chronic heart failure","volume":"344","author":"Eichhorn","year":"2001","journal-title":"ACC Curr. J. Rev."},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Meyers, T.A., Heitzman, J.A., and Townsend, D. (2019). Acute myocardial injury in mdx hearts ameliorated by ARB but not ACE inhibitor treatment, Submitted.","DOI":"10.1101\/765602"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.mayocp.2015.10.019","article-title":"Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blockers in Patients Without Heart Failure? Insights from 254,301 Patients from Randomized Trials","volume":"91","author":"Bangalore","year":"2016","journal-title":"Mayo Clin. Proc."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1016\/S0140-6736(00)02213-3","article-title":"Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: Randomised trial\u2014The Losartan Heart Failure Survival Study ELITE II","volume":"355","author":"Pitt","year":"2000","journal-title":"Lancet"},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Allen, H.D., Flanigan, K.M., Thrush, P.T., Viollet-Callendret, L., Dvorchik, I., Yin, H., Canter, C.E., Connolly, A.M., Parrish, M., and McDonald, C.M. (2013). A Randomized, Double-Blind Trial of Lisinopril and Losartan for the Treatment of Cardiomyopathy in Duchenne Muscular Dystrophy. PLoS Curr. Muscular Dystrophy, 5.","DOI":"10.1371\/currents.md.2cc69a1dae4be7dfe2bcb420024ea865"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1161\/01.HYP.32.3.387","article-title":"Pathways for angiotensin II generation in intact human tissue: Evidence from comparative pharmacological interruption of the renin system","volume":"32","author":"Hollenberg","year":"1998","journal-title":"Hypertension"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"3054","DOI":"10.2174\/1381612811319170012","article-title":"Non-ACE Pathway-induced Angiotensin II Production","volume":"19","author":"Uehara","year":"2013","journal-title":"Curr. Pharm. Des."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.jacc.2016.11.064","article-title":"Roles of Angiotensin Peptides and Recombinant Human ACE2 in Heart Failure","volume":"69","author":"Basu","year":"2017","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/ncb1137","article-title":"Mechanical stress activates angiotensin II type 1 receptor without the involvement of angiotensin II","volume":"6","author":"Zou","year":"2004","journal-title":"Nat. Cell Biol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1124\/mol.115.099176","article-title":"Structure-Function Basis of Attenuated Inverse Agonism of Angiotensin II Type 1 Receptor Blockers for Active-State Angiotensin II Type 1 Receptors","volume":"88","author":"Takezako","year":"2015","journal-title":"Mol. Pharmacol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1042\/CS20160243","article-title":"Angiotensin II type 2 receptor (AT2R) in renal and cardiovascular disease","volume":"130","author":"Chow","year":"2016","journal-title":"Clin. Sci."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1373\/clinchem.2017.278705","article-title":"Low- and high-renin heart failure phenotypes with clinical implications","volume":"64","author":"Pavo","year":"2018","journal-title":"Clin. Chem."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.amjcard.2012.02.064","article-title":"Effects of angiotensin-converting enzyme inhibitors and\/or beta blockers on the cardiomyopathy in Duchenne muscular dystrophy","volume":"110","author":"Viollet","year":"2012","journal-title":"Am. J. Cardiol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1161\/CIRCRESAHA.116.304678","article-title":"Role of Sodium and Calcium Dysregulation in Tachyarrhythmias in Sudden Cardiac Death","volume":"16","author":"Wagner","year":"2015","journal-title":"Circ. Res."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1016\/j.jacc.2009.05.015","article-title":"The Sympathetic Nervous System in Heart Failure. Physiology, Pathophysiology, and Clinical Implications","volume":"54","author":"Triposkiadis","year":"2009","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1253\/circj.70.991","article-title":"Beta-Blocker Therapy for Cardiac Dysfunction in Patients With Muscular Dystrophy","volume":"70","author":"Kajimoto","year":"2006","journal-title":"Circ. J."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.2169\/internalmedicine.49.3259","article-title":"Carvedilol can Prevent Cardiac Events in Duchenne Muscular Dystrophy","volume":"49","author":"Matsumura","year":"2010","journal-title":"Intern. Med."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S1474-4422(14)70318-7","article-title":"Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: A randomised, double-blind, placebo-controlled trial","volume":"14","author":"Raman","year":"2015","journal-title":"Lancet. Neurol."},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Janssen, P.M.L., Murray, J.D., Schill, K.E., Rastogi, N., Schultz, E.J., Tran, T., Raman, S.V., and Rafael-Fortney, J.A. (2014). Prednisolone attenuates improvement of cardiac and skeletal contractile function and histopathology by lisinopril and spironolactone in the mdx mouse model of duchenne muscular dystrophy. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0088360"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13023-017-0590-8","article-title":"Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: Results of a two-year open-label extension trial","volume":"12","author":"Raman","year":"2017","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1002\/mus.23831","article-title":"Corticosteroids in Duchenne muscular dystrophy: Major variations in practice","volume":"48","author":"Griggs","year":"2013","journal-title":"Muscle Nerve"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/j.pmr.2012.08.003","article-title":"Novel Approaches to Corticosteroid Treatment in Duchenne Muscular Dystrophy","volume":"23","author":"Hoffman","year":"2012","journal-title":"Phys. Med. Rehabil. Clin. N. Am."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1093\/eurjhf\/hfp028","article-title":"Contrasting effects of steroids and angiotensin-converting-enzyme inhibitors in a mouse model of dystrophin-deficient cardiomyopathy","volume":"11","author":"Bauer","year":"2009","journal-title":"Eur. J. Heart Fail."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1016\/j.jacc.2012.12.008","article-title":"All-cause mortality and cardiovascular outcomes with prophylactic steroid therapy in Duchenne muscular dystrophy","volume":"61","author":"Schram","year":"2013","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1007\/s00246-005-0909-4","article-title":"Steroid therapy and cardiac function in duchenne muscular dystrophy","volume":"26","author":"Markham","year":"2005","journal-title":"Pediatr. Cardiol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1016\/j.jpeds.2013.05.060","article-title":"Oral corticosteroids and onset of cardiomyopathy in Duchenne muscular dystrophy","volume":"163","author":"Barber","year":"2013","journal-title":"J. Pediatr."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/S0002-9149(02)03429-X","article-title":"Effects of deflazacort on left ventricular function in patients with Duchenne muscular dystrophy","volume":"91","author":"Silversides","year":"2003","journal-title":"Am. J. Cardiol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1161\/JAHA.115.001896","article-title":"Glucocorticoid Therapy for Duchenne Cardiomyopathy: A Hobson\u2019s Choice?","volume":"4","author":"Raman","year":"2015","journal-title":"J. Am. Heart Assoc."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/mus.22097","article-title":"Cardiomyopathy of Duchenne muscular dystrophy: Current understanding and future directions","volume":"44","author":"Spurney","year":"2011","journal-title":"Muscle Nerve"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1002\/emmm.201302621","article-title":"VBP15, a novel anti-inflammatory and membrane-stabilizer, improves muscular dystrophy without side effects","volume":"5","author":"Heier","year":"2013","journal-title":"EMBO Mol. Med."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"29","DOI":"10.3233\/JND-150113","article-title":"Current Translational Research and Murine Models For Duchenne Muscular Dystrophy","volume":"3","author":"Rodrigues","year":"2016","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1056\/NEJM198705073161904","article-title":"X-Linked dilated cardiomyopathy","volume":"316","author":"Berko","year":"1985","journal-title":"N. Engl. J. Med."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/S0960-8966(99)00015-2","article-title":"X-linked dilated cardiomyopathy and the dystrophin gene","volume":"9","author":"Ferlini","year":"1999","journal-title":"Neuromuscul. Disord."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"303","DOI":"10.3390\/ph8020303","article-title":"X-linked dilated cardiomyopathy: A cardiospecific phenotype of dystrophinopathy","volume":"8","author":"Nakamura","year":"2015","journal-title":"Pharmaceuticals"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1161\/CIRCGENETICS.109.867242","article-title":"Analysis of dystrophin deletion mutations predicts age of cardiomyopathy onset in becker muscular dystrophy","volume":"2","author":"Kaspar","year":"2009","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_167","first-page":"37","article-title":"Clinical potential of ataluren in the treatment of Duchenne muscular dystrophy","volume":"6","author":"Namgoong","year":"2016","journal-title":"Degener. Neurol. Neuromuscul. Dis."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/nature05756","article-title":"PTC124 targets genetic disorders caused by nonsense mutations","volume":"447","author":"Welch","year":"2007","journal-title":"Nature"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"316","DOI":"10.3389\/fped.2018.00316","article-title":"Off-Label Use of Ataluren in Four Non-ambulatory Patients With Nonsense Mutation Duchenne Muscular Dystrophy: Effects on Cardiac and Pulmonary Function and Muscle Strength","volume":"6","author":"Dillmann","year":"2018","journal-title":"Front. Pediatr."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1073\/pnas.0406700102","article-title":"Systemic delivery of antisense oligoribonucleotide restores dystrophin expression in body-wide skeletal muscles","volume":"102","author":"Lu","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1002\/ana.21627","article-title":"Efficacy of systemic morpholino exon-skipping in duchenne dystrophy dogs","volume":"65","author":"Yokota","year":"2009","journal-title":"Ann. Neurol."},{"key":"ref_172","first-page":"1202","article-title":"Antisense oligonucleotides for the treatment of cardiomyopathy in Duchenne muscular dystrophy","volume":"11","author":"Nguyen","year":"2019","journal-title":"Am. J. Transl. Res."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/gt.2009.120","article-title":"Dose-dependent restoration of dystrophin expression in cardiac muscle of dystrophic mice by systemically delivered morpholino","volume":"17","author":"Wu","year":"2010","journal-title":"Gene Ther."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"3909","DOI":"10.1093\/hmg\/ddn293","article-title":"Cell-penetrating peptide-conjugated antisense oligonucleotides restore systemic muscle and cardiac dystrophin expression and function","volume":"17","author":"Yin","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"e38","DOI":"10.1038\/mtna.2012.30","article-title":"Pip6-PMO, A New Generation of Peptide-oligonucleotide Conjugates With Improved Cardiac Exon Skipping Activity for DMD Treatment","volume":"1","author":"Betts","year":"2012","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"4213","DOI":"10.1073\/pnas.1613203114","article-title":"Effects of systemic multiexon skipping with peptide-conjugated morpholinos in the heart of a dog model of Duchenne muscular dystrophy","volume":"114","author":"Echigoya","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1002\/ana.24555","article-title":"Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy","volume":"79","author":"Mendell","year":"2016","journal-title":"Ann. Neurol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"R163","DOI":"10.1093\/hmg\/ddy171","article-title":"Exon-skipping advances for Duchenne muscular dystrophy","volume":"27","author":"Aupy","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1161\/CIRCULATIONAHA.117.028382","article-title":"Mutation-based therapy for duchenne muscular dystrophy: Antisense treatment arrives in the clinic","volume":"136","author":"McNally","year":"2017","journal-title":"Circulation"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1016\/j.ymthe.2017.02.019","article-title":"Progress toward Gene Therapy for Duchenne Muscular Dystrophy","volume":"25","author":"Chamberlain","year":"2017","journal-title":"Mol. Ther."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"2337","DOI":"10.1016\/j.ymthe.2018.07.011","article-title":"Systemic AAV Micro-dystrophin Gene Therapy for Duchenne Muscular Dystrophy","volume":"26","author":"Duan","year":"2018","journal-title":"Mol. Ther."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1038\/gt.2011.36","article-title":"Improvement of cardiac fibrosis in dystrophic mice by rAAV9-mediated microdystrophin transduction","volume":"18","author":"Shin","year":"2011","journal-title":"Gene Ther."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/nm1439","article-title":"rAAV6-microdystrophin preserves muscle function and extends lifespan in severely dystrophic mice","volume":"12","author":"Gregorevic","year":"2006","journal-title":"Nat. Med."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1038\/gt.2008.104","article-title":"Construction and analysis of compact muscle-specific promoters for AAV vectors","volume":"15","author":"Wang","year":"2008","journal-title":"Gene Ther."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1038\/sj.mt.6300027","article-title":"Design of tissue-specific regulatory cassettes for high-level rAAV-mediated expression in skeletal and cardiac muscle","volume":"15","author":"Salva","year":"2007","journal-title":"Mol. Ther."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.omtm.2017.06.006","article-title":"A Five-Repeat Micro-Dystrophin Gene Ameliorated Dystrophic Phenotype in the Severe DBA\/2J-mdx Model of Duchenne Muscular Dystrophy","volume":"6","author":"Hakim","year":"2017","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1089\/hgtb.2012.243","article-title":"Pre-existing Anti\u2013Adeno-Associated Virus Antibodies as a Challenge in AAV Gene Therapy","volume":"24","author":"Joergensen","year":"2013","journal-title":"Hum. Gene Ther. Methods"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1038\/mt.2013.244","article-title":"Plasmapheresis eliminates the negative impact of AAV antibodies on microdystrophin gene expression following vascular delivery","volume":"22","author":"Chicoine","year":"2014","journal-title":"Mol. Ther."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1146\/annurev-med-081117-010451","article-title":"CRISPR Correction of Duchenne Muscular Dystrophy","volume":"70","author":"Min","year":"2018","journal-title":"Annu. Rev. Med."},{"key":"ref_190","doi-asserted-by":"crossref","unstructured":"Lim, K.R.Q., Yoon, C., and Yokota, T. (2018). Applications of CRISPR\/Cas9 for the treatment of Duchenne muscular dystrophy. J. Pers. Med., 8.","DOI":"10.20944\/preprints201811.0018.v1"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1126\/science.aad5143","article-title":"In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy","volume":"351","author":"Nelson","year":"2016","journal-title":"Science"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1126\/science.aau1549","article-title":"Gene editing restores dystrophin expression in a canine model of Duchenne muscular dystrophy","volume":"362","author":"Amoasii","year":"2018","journal-title":"Science"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1126\/scitranslmed.aan8081","article-title":"Single-cut genome editing restores dystrophin expression in a new mouse model of muscular dystrophy","volume":"9","author":"Amoasii","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"ref_194","first-page":"1","article-title":"Muscle-specific CRISPR\/Cas9 dystrophin gene editing ameliorates pathophysiology in a mouse model for Duchenne muscular dystrophy","volume":"8","author":"Bengtsson","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1172\/jci.insight.124297","article-title":"AAV CRISPR editing rescues cardiac and muscle function for 18 months in dystrophic mice","volume":"3","author":"Hakim","year":"2018","journal-title":"JCI Insight"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ymthe.2019.05.001","article-title":"Life-Long AAV-Mediated CRISPR Genome Editing in Dystrophic Heart Improves Cardiomyopathy without Causing Serious Lesions in mdx Mice","volume":"27","author":"Xu","year":"2019","journal-title":"Mol. Ther."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1038\/s41591-019-0344-3","article-title":"Long-term evaluation of AAV-CRISPR genome editing for Duchenne muscular dystrophy","volume":"25","author":"Nelson","year":"2019","journal-title":"Nat. Med."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1126\/science.aad5725","article-title":"Postnatal genome editing partially restores dystrophin expression in a mouse model of muscular dystrophy","volume":"351","author":"Long","year":"2016","journal-title":"Science"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1038\/nbt.2623","article-title":"High-frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells","volume":"31","author":"Fu","year":"2013","journal-title":"Nat. Biotechnol."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1038\/nature16526","article-title":"High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects","volume":"529","author":"Kleinstiver","year":"2016","journal-title":"Nature"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/17\/4098\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:13:00Z","timestamp":1760188380000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/17\/4098"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,22]]},"references-count":200,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2019,9]]}},"alternative-id":["ijms20174098"],"URL":"https:\/\/doi.org\/10.3390\/ijms20174098","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,22]]}}}