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Therapy Insight: cardiovascular complications associated with muscular dystrophies

Nature Clinical Practice Cardiovascular Medicine volume 2, pages 301–308 (2005)Cite this article

Abstract

The muscular dystrophies are commonly associated with cardiovascular complications, including cardiomyopathy and cardiac arrhythmias. These complications are caused by intrinsic defects in cardiomyocyte and cardiac conduction system function, and by the presence of severe skeletal muscle disease, which also contributes to cardiac dysfunction. Unlike the skeletal muscle degenerative process, for which treatment options are currently limited, therapy is available for the cardiovascular complications that accompany muscular dystrophy. New therapies for skeletal muscle degeneration are moving into clinical trials and, ultimately, into clinical practice. These therapies are expected to also improve the cardiac function, longevity and wellbeing of muscular dystrophy patients.

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Figure 1: Membrane-associated proteins in skeletal myofibers.
Figure 2: Muscle regeneration.

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References

  1. Laval SH and Bushby KM (2004) Limb-girdle muscular dystrophies—from genetics to molecular pathology. Neuropathol Appl Neurobiol 30: 91–105

    Article  CAS  Google Scholar 

  2. Lapidos KA et al. (2004) The dystrophin glycoprotein complex: signaling strength and integrity for the sarcolemma. Circ Res 94: 1023–1031

    Article  CAS  Google Scholar 

  3. Blake DJ and Martin-Rendon E (2002) Intermediate filaments and the function of the dystrophin-protein complex. Trends Cardiovasc Med 12: 224–228

    Article  CAS  Google Scholar 

  4. Petrof BJ et al. (1993) Dystrophin protects the sarcolemma from stresses developed during muscle contraction. Proc Natl Acad Sci U S A 90: 3710–3714

    Article  CAS  Google Scholar 

  5. Danialou G et al. (2001) Dystrophin-deficient cardiomyocytes are abnormally vulnerable to mechanical stress-induced contractile failure and injury. Faseb J 15: 1655–1657

    Article  CAS  Google Scholar 

  6. Dellorusso C et al. (2001) Tibialis anterior muscles in mdx mice are highly susceptible to contraction-induced injury. J Muscle Res Cell Motil 22: 467–475

    Article  CAS  Google Scholar 

  7. Hack AA et al. (1999) Muscle degeneration without mechanical injury in sarcoglycan deficiency. Proc Natl Acad Sci U S A 96: 10723–10728

    Article  CAS  Google Scholar 

  8. Badorff C et al. (2000) Enteroviral protease 2A directly cleaves dystrophin and is inhibited by a dystrophin-based substrate analogue. J Biol Chem 275: 11191–11197

    Article  CAS  Google Scholar 

  9. Matsuda R et al. (1995) Visualization of dystrophic muscle fibers in mdx mouse by vital staining with Evans blue: evidence of apoptosis in dystrophin-deficient muscle. J Biochem (Tokyo) 118: 959–964

    Article  CAS  Google Scholar 

  10. McLaurin MD et al. (1997) Cardiac troponin I, cardiac troponin T, and creatine kinase MB in dialysis patients without ischemic heart disease: evidence of cardiac troponin T expression in skeletal muscle. Clin Chem 43: 976–982

    CAS  PubMed  Google Scholar 

  11. Saggin L et al. (1990) Cardiac troponin T in developing, regenerating and denervated rat skeletal muscle. Development 110: 547–554

    CAS  PubMed  Google Scholar 

  12. Porter JD et al. (2002) A chronic inflammatory response dominates the skeletal muscle molecular signature in dystrophin-deficient mdx mice. Hum Mol Genet 11: 263–272

    Article  CAS  Google Scholar 

  13. Wehling-Henricks M et al. (2004) Prednisolone decreases cellular adhesion molecules required for inflammatory cell infiltration in dystrophin-deficient skeletal muscle. Neuromuscul Disord 14: 483–490

    Article  Google Scholar 

  14. Thomas GD et al. (1998) Impaired metabolic modulation of alpha-adrenergic vasoconstriction in dystrophin-deficient skeletal muscle. Proc Natl Acad Sci U S A 95: 15090–15095

    Article  CAS  Google Scholar 

  15. Sander M et al. (2000) Functional muscle ischemia in neuronal nitric oxide synthase-deficient skeletal muscle of children with Duchenne muscular dystrophy. Proc Natl Acad Sci U S A 97: 13818–13823

    Article  CAS  Google Scholar 

  16. Coral-Vazquez R et al. (1999) Disruption of the sarcoglycan-sarcospan complex in vascular smooth muscle: a novel mechanism for cardiomyopathy and muscular dystrophy. Cell 98: 465–474

    Article  CAS  Google Scholar 

  17. Wheeler MT et al. (2004) Smooth muscle cell-extrinsic vascular spasm arises from cardiomyocyte degeneration in sarcoglycan-deficient cardiomyopathy. J Clin Invest 113: 668–675

    Article  CAS  Google Scholar 

  18. Moreira ES et al. (2000) Limb-girdle muscular dystrophy type 2G is caused by mutations in the gene encoding the sarcomeric protein telethonin. Nat Genet 24: 163–166

    Article  CAS  Google Scholar 

  19. Hauser MA et al. (2000) Myotilin is mutated in limb girdle muscular dystrophy 1A. Hum Mol Genet 9: 2141–2147

    Article  CAS  Google Scholar 

  20. Hackman P et al. (2002) Tibial muscular dystrophy is a titinopathy caused by mutations in TTN, the gene encoding the giant skeletal-muscle protein titin. Am J Hum Genet 71: 492–500

    Article  CAS  Google Scholar 

  21. Knoll R et al. (2002) The cardiac mechanical stretch sensor machinery involves a Z disc complex that is defective in a subset of human dilated cardiomyopathy. Cell 111: 943–955

    Article  CAS  Google Scholar 

  22. Omens JH et al. (2002) Muscle LIM protein deficiency leads to alterations in passive ventricular mechanics. Am J Physiol Heart Circ Physiol 282: H680–H687

    Article  CAS  Google Scholar 

  23. Arber S et al. (1997) MLP-deficient mice exhibit a disruption of cardiac cytoarchitectural organization, dilated cardiomyopathy, and heart failure. Cell 88: 393–403

    Article  CAS  Google Scholar 

  24. Muntoni F et al. (2004) Defective glycosylation in congenital muscular dystrophies. Curr Opin Neurol 17: 205–209

    Article  CAS  Google Scholar 

  25. Brockington M et al. (2001) Mutations in the fukutin-related protein gene (FKRP) identify limb girdle muscular dystrophy 2I as a milder allelic variant of congenital muscular dystrophy MDC1C. Hum Mol Genet 10: 2851–2859

    Article  CAS  Google Scholar 

  26. Barresi R et al. (2004) LARGE can functionally bypass alpha-dystroglycan glycosylation defects in distinct congenital muscular dystrophies. Nat Med 10: 696–703

    Article  CAS  Google Scholar 

  27. Ostlund C and Worman HJ (2003) Nuclear envelope proteins and neuromuscular diseases. Muscle Nerve 27: 393–406

    Article  CAS  Google Scholar 

  28. van Berlo JH et al. (2005) Meta-analysis of clinical characteristics of 299 carriers of LMNA gene mutations: do lamin A/C mutations portend a high risk of sudden death? J Mol Med 83: 79–83

    Article  Google Scholar 

  29. Bashir R et al. (1998) A gene related to Caenorhabditis elegans spermatogenesis factor fer-1 is mutated in limb-girdle muscular dystrophy type 2B. Nat Genet 20: 37–42

    Article  CAS  Google Scholar 

  30. Anderson LV et al. (1999) Dysferlin is a plasma membrane protein and is expressed early in human development. Hum Mol Genet 8: 855–861

    Article  CAS  Google Scholar 

  31. Davis DB et al. (2002) Calcium-sensitive phospholipid binding properties of normal and mutant ferlin C2 domains. J Biol Chem 277: 22883–22888

    Article  CAS  Google Scholar 

  32. Liu J et al. (1998) Dysferlin, a novel skeletal muscle gene, is mutated in Miyoshi myopathy and limb girdle muscular dystrophy. Nat Genet 20: 31–36

    Article  CAS  Google Scholar 

  33. Bansal D et al. (2003) Defective membrane repair in dysferlin-deficient muscular dystrophy. Nature 423: 168–172

    Article  CAS  Google Scholar 

  34. Fanin M et al. (2001) Calpain-3 and dysferlin protein screening in patients with limb-girdle dystrophy and myopathy. Neurology 56: 660–665

    Article  CAS  Google Scholar 

  35. Matsuda C et al. (2001) The sarcolemmal proteins dysferlin and caveolin-3 interact in skeletal muscle. Hum Mol Genet 10: 1761–1766

    Article  CAS  Google Scholar 

  36. Woodman SE et al. (2004) Caveolinopathies: mutations in caveolin-3 cause four distinct autosomal dominant muscle diseases. Neurology 62: 538–543

    Article  CAS  Google Scholar 

  37. Bushby K et al. (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  Google Scholar 

  38. Muntoni F (2003) Cardiomyopathy in muscular dystrophies. Curr Opin Neurol 16: 577–583

    Article  Google Scholar 

  39. McGeachie JK and Grounds MD (1999) The timing between skeletal muscle myoblast replication and fusion into myotubes, and the stability of regenerated dystrophic myofibres: an autoradiographic study in mdx mice. J Anat 194: 287–295

    Article  Google Scholar 

  40. Manasek FJ (1968) Mitosis in developing cardiac muscle. J Cell Biol 37: 191–196

    Article  CAS  Google Scholar 

  41. Beltrami AP et al. (2003) Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 114: 763–776

    Article  CAS  Google Scholar 

  42. Hunt SA et al. (2001) ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult: Executive Summary A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure): Developed in Collaboration With the International Society for Heart and Lung Transplantation; Endorsed by the Heart Failure Society of America. Circulation 104: 2996–3007

    Article  CAS  Google Scholar 

  43. Duboc D et al. (2005) Effect of perindopril on the onset and progression of left ventricular dysfunction in Duchenne muscular dystrophy. J Am Coll Cardiol 45: 855–857

    Article  CAS  Google Scholar 

  44. Melacini P et al. (1998) Cardiac transplantation in a Duchenne muscular dystrophy carrier. Neuromuscul Disord 8: 585–590

    Article  CAS  Google Scholar 

  45. Rees W et al. (1993) Heart transplantation in patients with muscular dystrophy associated with end-stage cardiomyopathy. J Heart Lung Transplant 12: 804–807

    CAS  PubMed  Google Scholar 

  46. Corrado G et al. (2002) Prognostic value of electrocardiograms, ventricular late potentials, ventricular arrhythmias, and left ventricular systolic dysfunction in patients with Duchenne muscular dystrophy. Am J Cardiol 89: 838–841

    Article  Google Scholar 

  47. Groh WJ et al. (2002) Severity of cardiac conduction involvement and arrhythmias in myotonic dystrophy type 1 correlates with age and CTG repeat length. J Cardiovasc Electrophysiol 13: 444–448

    Article  Google Scholar 

  48. Ranum LP and Day JW (2002) Myotonic dystrophy: clinical and molecular parallels between myotonic dystrophy type 1 and type 2. Curr Neurol Neurosci Rep 2: 465–470

    Article  Google Scholar 

  49. Schoser BG et al. (2004) Sudden cardiac death in myotonic dystrophy type 2. Neurology 63: 2402–2404

    Article  CAS  Google Scholar 

  50. Gregoratos G et al. (2002) ACC/AHA/NASPE 2002 guideline update for implantation of cardiac pacemakers and antiarrhythmia devices: summary article. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/NASPE Committee to Update the 1998 Pacemaker Guidelines). J Cardiovasc Electrophysiol 13: 1183–1199

    Article  Google Scholar 

  51. Finder JD et al. (2004) Respiratory care of the patient with Duchenne muscular dystrophy: ATS consensus statement. Am J Respir Crit Care Med 170: 456–465

    Article  Google Scholar 

  52. Gregorevic P et al. (2004) Systemic delivery of genes to striated muscles using adeno-associated viral vectors. Nat Med 10: 828–834

    Article  CAS  Google Scholar 

  53. Gussoni E et al. (1999) Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature 401: 390–394

    CAS  Google Scholar 

  54. LaBarge MA and Blau HM (2002) Biological progression from adult bone marrow to mononucleate muscle stem cell to multinucleate muscle fiber in response to injury. Cell 111: 589–601

    Article  CAS  Google Scholar 

  55. Barton ER et al. (2002) Muscle-specific expression of insulin-like growth factor I counters muscle decline in mdx mice. J Cell Biol 157: 137–148

    Article  CAS  Google Scholar 

  56. Bogdanovich S et al. (2002) Functional improvement of dystrophic muscle by myostatin blockade. Nature 420: 418–421

    Article  CAS  Google Scholar 

  57. Krag TO et al. (2004) Heregulin ameliorates the dystrophic phenotype in mdx mice. Proc Natl Acad Sci U S A 101: 13856–13860

    Article  CAS  Google Scholar 

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Acknowledgements

EMM is supported by the Muscular Dystrophy Association, the NIH and the Burroughs Wellcome Fund.

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Authors and Affiliations

  1. Departments of Medicine and Human Genetics,

    Elizabeth M McNally & Heather MacLeod

  2. Department of Medicine, at the University of Chicago, IL, USA

    Elizabeth M McNally & Heather MacLeod

Authors
  1. Elizabeth M McNally
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  2. Heather MacLeod
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Corresponding author

Correspondence to Elizabeth M McNally.

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The authors declare no competing financial interests.

Glossary

DYSTROPHIN–GLYCOPROTEIN COMPLEX

A macromolecular complex important for membrane stability and interactions with the extracellular matrix

SARCOGLYCAN

The sarcoglycan subunits α, β, γ and δ are part of the dystrophin–glycoprotein complex

TELETHONIN

Mutations in telethonin lead to muscular dystrophy; together with titin, telethonin is thought to be important for passive stretch in cardiomyocytes

TITIN

A giant protein that spans the length of the sarcomere and is thought to be important for elastic recoil of muscle

MYOTILIN

A protein found at the Z band; mutations in myotilin lead to muscular dystrophy

FUKUTIN RELATED PROTEIN

A protein thought to have glyosylation functions that are important for membrane-matrix interactions

KYPHOSCOLIOSIS

A combination of backward (kyphosis) and lateral (scoliosis) curvature of the spinal column

HEREGULIN

An extracellular matrix protein that is involved in neuromuscular junction function

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McNally, E., MacLeod, H. Therapy Insight: cardiovascular complications associated with muscular dystrophies. Nat Rev Cardiol 2, 301–308 (2005). https://doi.org/10.1038/ncpcardio0213

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