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Cardiomyopathy in Duchenne muscular dystrophy: pathogenesis and therapeutics

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Abstract

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder caused by the absence of dystrophin, a sarcolemmal protein which links the cytoskeleton to the extracellular matrix by interacting with a large number of proteins. Heart failure is a classic complication of this disease. The authors review the pathogenesis and therapeutics of cardiac involvement in DMD.

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References

  1. Finsterer J, Stollberger C (2003) The heart in human dystrophinopathies. Cardiology 99(1):1–19

    Article  PubMed  Google Scholar 

  2. Lapidos KA, Kakkar R, McNally EM (2004) The dystrophin glycoprotein complex: signaling strength and integrity for the sarcolemma. Circ Res 94(8):1023–1031

    Article  CAS  PubMed  Google Scholar 

  3. Rybakova IN, Patel JR, Ervasti JM (2000) The dystrophin complex forms a mechanically strong link between the sarcolemma and costameric actin. J Cell Biol 150(5):1209–1214

    Article  CAS  PubMed  Google Scholar 

  4. Goodwin FC, Muntoni F (2005) Cardiac involvement in muscular dystrophies: molecular mechanisms. Muscle Nerve 32(5):577–588

    Article  CAS  PubMed  Google Scholar 

  5. Colan SD (2005) Evolving therapeutic strategies for dystrophinopathies: potential for conflict between cardiac and skeletal needs. Circulation 112(18):2756–2758

    Article  PubMed  Google Scholar 

  6. Kamogawa Y, Biro S, Maeda M, Setoguchi M, Hirakawa T, Yoshida H, Tei C (2001) Dystrophin-deficient myocardium is vulnerable to pressure overload in vivo. Cardiovasc Res 50(3):509–515

    Article  CAS  PubMed  Google Scholar 

  7. Sicinski P, Geng Y, Ryder-Cook AS, Barnard EA, Darlison MG, Barnard PJ (1989) The molecular basis of muscular dystrophy in the mdx mouse: a point mutation. Science 244(4912):1578–1580

    Article  CAS  PubMed  Google Scholar 

  8. Wehling-Henricks M, Jordan MC, Roos KP, Deng B, Tidball JG (2005) Cardiomyopathy in dystrophin-deficient hearts is prevented by expression of a neuronal nitric oxide synthase transgene in the myocardium. Hum Mol Genet 14(14):1921–1933

    Article  CAS  PubMed  Google Scholar 

  9. Williams IA, Allen DG (2007) Intracellular calcium handling in ventricular myocytes from mdx mice. Am J Physiol Heart Circ Physiol 292(2):H846–H855

    Article  CAS  PubMed  Google Scholar 

  10. Whitehead NP, Yeung EW, Allen DG (2006) Muscle damage in mdx (dystrophic) mice: role of calcium and reactive oxygen species. Clin Exp Pharmacol Physiol 33(7):657–662

    Article  CAS  PubMed  Google Scholar 

  11. Manzur AY, Kuntzer T, Pike M, Swan A (2008) Glucocorticoid corticosteroids for Duchenne muscular dystrophy. Cochrane Database Syst Rev (1):CD003725

  12. Welch EM, Barton ER, Zhuo J, Tomizawa Y, Friesen WJ, Trifillis P, Paushkin S, Patel M, Trotta CR, Hwang S, Wilde RG, Karp G, Takasugi J, Chen G, Jones S, Ren H, Moon YC, Corson D, Turpoff AA, Campbell JA, Conn MM, Khan A, Almstead NG, Hedrick J, Mollin A, Risher N, Weetall M, Yeh S, Branstrom AA, Colacino JM, Babiak J, Ju WD, Hirawat S, Northcutt VJ, Miller LL, Spatrick P, He F, Kawana M, Feng H, Jacobson A, Peltz SW, Sweeney HL (2007) PTC124 targets genetic disorders caused by nonsense mutations. Nature 447(7140):87–91

    Article  CAS  PubMed  Google Scholar 

  13. Bonuccelli G, Sotgia F, Schubert W, Park DS, Frank PG, Woodman SE, Insabato L, Cammer M, Minetti C, Lisanti MP (2003) Proteasome inhibitor (MG-132) treatment of mdx mice rescues the expression and membrane localization of dystrophin and dystrophin-associated proteins. Am J Pathol 163(4):1663–1675

    CAS  PubMed  Google Scholar 

  14. Brunelli S, Sciorati C, D’Antona G, Innocenzi A, Covarello D, Galvez BG, Perrotta C, Monopoli A, Sanvito F, Bottinelli R, Ongini E, Cossu G, Clementi E (2007) Nitric oxide release combined with nonsteroidal anti-inflammatory activity prevents muscular dystrophy pathology and enhances stem cell therapy. Proc Natl Acad Sci USA 104(1):264–269

    Article  CAS  PubMed  Google Scholar 

  15. Minetti GC, Colussi C, Adami R, Serra C, Mozzetta C, Parente V, Fortuni S, Straino S, Sampaolesi M, Di Padova M, Illi B, Gallinari P, Steinkühler C, Capogrossi MC, Sartorelli V, Bottinelli R, Gaetano C, Puri PL (2006) Functional and morphological recovery of dystrophic muscles in mice treated with deacetylase inhibitors. Nat Med 12(10):1147–1150

    Article  CAS  PubMed  Google Scholar 

  16. Ogata H, Ishikawa Y, Ishikawa Y, Minami R (2009) Beneficial effects of beta-blockers and angiotensin-converting enzyme inhibitors in Duchenne muscular dystrophy. J Cardiol 53(1):72–78

    Article  PubMed  Google Scholar 

  17. Duboc D, Meune C, Lerebours G, Devaux JY, Vaksmann G, Bécane HM (2005) Effect of perindopril on the onset and progression of left ventricular dysfunction in Duchenne muscular dystrophy. J Am Coll Cardiol 45(6):855–857

    Article  CAS  PubMed  Google Scholar 

  18. Task Force for Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of European Society of Cardiology, Dickstein K, Cohen-Solal A, Filippatos G, McMurray JJ, Ponikowski P, Poole-Wilson PA, Strömberg A, van Veldhuisen DJ, Atar D, Hoes AW, Keren A, Mebazaa A, Nieminen M, Priori SG, Swedberg K; ESC Committee for Practice Guidelines, Vahanian A, Camm J, De Caterina R, Dean V, Dickstein K, Filippatos G, Funck-Brentano C, Hellemans I, Kristensen SD, McGregor K, Sechtem U, Silber S, Tendera M, Widimsky P, Zamorano JL (2008) ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the task force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European society of cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J 29(19):2388–2442

    Google Scholar 

  19. Delcayre C, Swynghedauw B (2002) Molecular mechanisms of myocardial remodeling. The role of aldosterone. J Mol Cell Cardiol 34(12):1577–1584

    Article  CAS  PubMed  Google Scholar 

  20. Jefferies JL, Eidem BW, Belmont JW, Craigen WJ, Ware SM, Fernbach SD, Neish SR, Smith EO, Towbin JA (2005) Genetic predictors and remodelling of dilated cardiomyopathy in muscular dystrophy. Circulation 112(18):2799–2804

    Article  PubMed  Google Scholar 

  21. Packer M, Coats AJ, Fowler MB, Katus HA, Krum H, Mohacsi P, Rouleau JL, Tendera M, Castaigne A, Roecker EB, Schultz MK, DeMets DL, Carvedilol Prospective Randomized Cumulative Survival Study Group (2001) Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med 344(22):1651–1658

    Article  CAS  PubMed  Google Scholar 

  22. Bushby K, Muntoni F, Bourke JP (2003) 107th ENMC international workshop: the management of cardiac involvement in muscular dystrophy and myotonic dystrophy. 7th–9th June 2002, Naarden, The Netherlands. Neuromuscul Disord 13:166–172

    Article  CAS  PubMed  Google Scholar 

  23. Bader H, Garrigue S, Lafitte S, Reuter S, Jaïs P, Haïssaguerre M, Bonnet J, Clementy J, Roudaut R (2004) Intra-left ventricular electromechanical asynchrony. A new independent predictor of severe cardiac events in heart failure patients. J Am Coll Cardiol 43(2):248–256

    Article  PubMed  Google Scholar 

  24. Aartsma-Rus A, Fokkema I, Verschuuren J, Ginjaar I, van Deutekom J, van Ommen GJ, den Dunnen JT (2009) Theoretic applicability of antisense-mediated exon skipping for Duchenne muscular dystrophy mutations. Hum Mutat 30(3):293–299

    Article  PubMed  Google Scholar 

  25. Wang Z, Kuhr CS, Allen JM, Blankinship M, Gregorevic P, Chamberlain JS, Tapscott SJ, Storb R (2007) Sustained AAV-mediated dystrophin expression in a canine model of Duchenne muscular dystrophy with a brief course of immunosuppression. Mol Ther 15(6):1160–1166

    CAS  PubMed  Google Scholar 

  26. Skuk D, Roy B, Goulet M, Chapdelaine P, Bouchard JP, Roy R, Dugré FJ, Lachance JG, Deschênes L, Hélène S, Sylvain M, Tremblay JP (2004) Dystrophin expression in myofibers of Duchenne muscular dystrophy patients following intramuscular injections of normal myogenic cells. Mol Ther 9(3):475–482

    Article  CAS  PubMed  Google Scholar 

  27. Townsend D, Yasuda S, Li S, Chamberlain JS, Metzger JM (2008) Emergent dilated cardiomyopathy caused by targeted repair of dystrophic skeletal muscle. Mol Ther 16(5):832–835

    Article  CAS  PubMed  Google Scholar 

  28. Lu QL, Mann CJ, Lou F, Bou-Gharios G, Morris GE, Xue SA, Fletcher S, Partridge TA, Wilton SD (2003) Functional amounts of dystrophin produced by skipping the mutated exon in the mdx dystrophic mouse. Nat Med 9(8):1009–1014

    Article  CAS  PubMed  Google Scholar 

  29. McClorey G, Fletcher S, Wilton S (2005) Splicing intervention for Duchenne muscular dystrophy. Curr Opin Pharmacol 5(5):529–534

    Article  CAS  PubMed  Google Scholar 

  30. Amalfitano A, Parks RJ (2002) Separating fact from fiction: assessing the potential of modified adenovirus vectors for use in human gene therapy. Curr Gene Ther 2(2):111–133

    Article  CAS  PubMed  Google Scholar 

  31. Gregorevic P, Blankinship MJ, Allen JM, Chamberlain JS (2008) Systemic microdystrophin gene delivery improves skeletal muscle structure and function in old dystrophic mdx mice. Mol Ther 16(4):657–664

    Article  CAS  PubMed  Google Scholar 

  32. Zhang G, Ludtke JJ, Thioudellet C, Kleinpeter P, Antoniou M, Herweijer H, Braun S, Wolff JA (2004) Intra-arterial delivery of naked plasmid DNA expressing full-length mouse dystrophin in the mdx mouse model of duchenne muscular dystrophy. Hum Gene Ther 15(8):770–782

    Article  CAS  PubMed  Google Scholar 

  33. Muntoni F, Wells D (2007) Genetic treatments in muscular dystrophies. Curr Opin Neurol 20(5):590–594

    Article  CAS  PubMed  Google Scholar 

  34. Sampaolesi M, Blot S, D’Antona G, Granger N, Tonlorenzi R, Innocenzi A, Mognol P, Thibaud JL, Galvez BG, Barthélémy I, Perani L, Mantero S, Guttinger M, Pansarasa O, Rinaldi C, Cusella De Angelis MG, Torrente Y, Bordignon C, Bottinelli R, Cossu G (2006) Mesoangioblast stem cells ameliorate muscle function in dystrophic dogs. Nature 444(7119):574–579

    Article  CAS  PubMed  Google Scholar 

  35. Bostick B, Yue Y, Long C, Marschalk N, Fine DM, Chen J, Duan D (2009) Cardiac expression of a mini-dystrophin that normalizes skeletal muscle force only partially restores heart function in aged Mdx mice. Mol Ther 17(2):253–261

    Article  CAS  PubMed  Google Scholar 

  36. Péault B, Rudnicki M, Torrente Y, Cossu G, Tremblay JP, Partridge T, Gussoni E, Kunkel LM, Huard J (2007) Stem and progenitor cells in skeletal muscle development, maintenance, and therapy. Mol Ther 15(5):867–877

    Article  PubMed  Google Scholar 

  37. Torrente Y, Belicchi M, Marchesi C, Dantona G, Cogiamanian F, Pisati F, Gavina M, Giordano R, Tonlorenzi R, Fagiolari G, Lamperti C, Porretti L, Lopa R, Sampaolesi M, Vicentini L, Grimoldi N, Tiberio F, Songa V, Baratta P, Prelle A, Forzenigo L, Guglieri M, Pansarasa O, Rinaldi C, Mouly V, Butler-Browne GS, Comi GP, Biondetti P, Moggio M, Gaini SM, Stocchetti N, Priori A, D’Angelo MG, Turconi A, Bottinelli R, Cossu G, Rebulla P, Bresolin N (2007) Autologous transplantation of muscle-derived CD133 + stem cells in Duchenne muscle patients. Cell Trans 16(6):563–577

    CAS  Google Scholar 

  38. Sampaolesi M, Torrente Y, Innocenzi A, Tonlorenzi R, D’Antona G, Pellegrino MA, Barresi R, Bresolin N, De Angelis MG, Campbell KP, Bottinelli R, Cossu G (2003) Cell therapy of alpha-sarcoglycan null dystrophic mice through intra-arterial delivery of mesoangioblasts. Science 301(5632):487–492

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

Thanks to Talia Ben-Jacob, MD, Cooper University hospital (Camden, New Jersey) for the rereading of this manuscript.

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Authors and Affiliations

  1. University of Medicine and Dentistry of New Jersey, Camden, NJ, USA

    Abdallah Fayssoil

  2. Intensive Care Unit, Raymond Poincaré Hospital, AP-HP, Garches, France

    Olivier Nardi, David Orlikowski & Djillali Annane

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  1. Abdallah Fayssoil
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  2. Olivier Nardi
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Correspondence to Abdallah Fayssoil.

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Fayssoil, A., Nardi, O., Orlikowski, D. et al. Cardiomyopathy in Duchenne muscular dystrophy: pathogenesis and therapeutics. Heart Fail Rev 15, 103–107 (2010). https://doi.org/10.1007/s10741-009-9156-8

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