Journal of Molecular and Cellular Cardiology
Volume 43, Issue 2 , Pages 119-129 , August 2007

Metabolic and signaling alterations in dystrophin-deficient hearts precede overt cardiomyopathy

  • Maya Khairallah

      Affiliations

    • Montreal Heart Institute and University of Montreal, 5000 Belanger St., Montreal, Quebec, Canada H1T 1C8
    • Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada H3A 1A1
    • ,
  • Ramzi Khairallah

      Affiliations

    • Montreal Heart Institute and University of Montreal, 5000 Belanger St., Montreal, Quebec, Canada H1T 1C8
    • ,
  • Martin E. Young

      Affiliations

    • Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA
    • ,
  • Jason R.B. Dyck

      Affiliations

    • Departments of Pediatrics and Pharmacology, University of Alberta, Edmonton, Alberta, Canada T6G 2S2
    • ,
  • Basil J. Petrof

      Affiliations

    • Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada H3A 1A1
    • ,
  • Christine Des Rosiers

      Affiliations

    • Montreal Heart Institute and University of Montreal, 5000 Belanger St., Montreal, Quebec, Canada H1T 1C8
    • Corresponding Author InformationCorresponding author. Tel.: +1 514 376 3330x3594; fax: +1 514 376 1355.

Received 7 March 2007 ,Revised 20 April 2007 ,Accepted 14 May 2007.

References 

  1. Acharyya S, Butchbach ME, Sahenk Z, Wang H, Saji M, Carathers M, et al. Dystrophin glycoprotein complex dysfunction: a regulatory link between muscular dystrophy and cancer cachexia. Cancer Cell. 2005;8:421–432
  2. Ally A, Park G. Rapid determination of creatine, phosphocreatine, purine bases and nucleotides (ATP, ADP, AMP, GTP, GDP) in heart biopsies by gradient ion-pair reversed-phase liquid chromatography. J. Chromatogr. 1992;575:19–27
  3. Altarejos JY, Taniguchi M, Clanachan AS, Lopaschuk GD. Myocardial ischemia differentially regulates LKB1 and an alternate 5′-AMP-activated protein kinase kinase. J. Biol. Chem. 2005;280:183–190
  4. Badorff C, Lee GH, Lamphear BJ, Martone ME, Campbell KP, Rhoads RE, et al. Enteroviral protease 2A cleaves dystrophin: evidence of cytoskeletal disruption in an acquired cardiomyopathy. Nat. Med. 1999;5:320–326
  5. Bia BL, Cassidy PJ, Young ME, Rafael JA, Leighton B, Davies KE, et al. Decreased myocardial nNOS, increased iNOS and abnormal ECGs in mouse models of Duchenne muscular dystrophy. J. Mol. Cell. Cardiol. 1999;31:1857–1862
  6. Chan AY, Soltys CL, Young ME, Proud CG, Dyck JR. Activation of AMP-activated protein kinase inhibits protein synthesis associated with hypertrophy in the cardiac myocyte. J. Biol. Chem. 2004;279:32771–32779
  7. Chapman-Smith A, Booker GW, Clements PR, Wallace JC, Keech DB. Further studies on the localization of the reactive lysyl residue of pyruvate carboxylase. Biochem. J. 1991;276(Pt 3):759–764
  8. Crilley JG, Boehm EA, Blair E, Rajagopalan B, Blamire AM, Styles P, et al. Hypertrophic cardiomyopathy due to sarcomeric gene mutations is characterized by impaired energy metabolism irrespective of the degree of hypertrophy. J. Am. Coll. Cardiol. 2003;41:1776–1782
  9. Danialou G, Comtois AS, Dudley R, Karpati G, Vincent G, Des Rosiers C, et al. Dystrophin-deficient cardiomyocytes are abnormally vulnerable to mechanical stress-induced contractile failure and injury. FASEB J. 2001;15:1655–1657
  10. Depre C, Vanoverschelde JL, Taegtmeyer H. Glucose for the heart. Circulation. 1999;99:578–588
  11. Duboc D, Meune C, Lerebours G, Devaux JY, Vaksmann G, Becane HM. Effect of perindopril on the onset and progression of left ventricular dysfunction in Duchenne muscular dystrophy. J. Am. Coll. Cardiol. 2005;45:855–857
  12. Dudley RW, Danialou G, Govindaraju K, Lands L, Eidelman DE, Petrof BJ. Sarcolemmal damage in dystrophin deficiency is modulated by synergistic interactions between mechanical and oxidative/nitrosative stresses. Am. J. Pathol. 2006;168:1276–1287
  13. Dunn JF, Raddam GK. Total ion content of skeletal and cardiac muscle in the mdx mouse dystrophy: Ca2+ is elevated at all ages. J. Neurol. Sci. 1991;103:226–231
  14. Feng J, Yan J, Buzin CH, Towbin JA, Sommer SS. Mutations in the dystrophin gene are associated with sporadic dilated cardiomyopathy. Mol. Genet. Metab. 2002;77:119–126
  15. Flogel U, Laussmann T, Godecke A, Abanador N, Schafers M, Fingas CD, et al. Lack of myoglobin causes a switch in cardiac substrate selection. Circ. Res. 2005;96:e68–e75
  16. Gibala MJ, Young ME, Taegtmeyer H. Anaplerosis of the citric acid cycle: role in energy metabolism of heart and skeletal muscle. Acta Physiol. Scand. 2000;168:657–665
  17. Hainsey TA, Senapati S, Kuhn DE, Rafael JA. Cardiomyopathic features associated with muscular dystrophy are independent of dystrophin absence in cardiovasculature. Neuromuscul. Disord. 2003;13:294–302
  18. Heydemann A, Huber JM, Kakkar R, Wheeler MT, McNally EM. Functional nitric oxide synthase mislocalization in cardiomyopathy. J. Mol. Cell. Cardiol. 2004;36:213–223
  19. Hopkins TA, Sugden MC, Holness MJ, Kozak R, Dyck JR, Lopaschuk GD. Control of cardiac pyruvate dehydrogenase activity in peroxisome proliferator-activated receptor-alpha transgenic mice. Am. J. Physiol.: Heart Circ. Physiol. 2003;285:H270–H276
  20. Huss JM, Kelly DP. Mitochondrial energy metabolism in heart failure: a question of balance. J. Clin. Invest. 2005;115:547–555
  21. Kaprielian RR, Severs NJ. Dystrophin and the cardiomyocyte membrane cytoskeleton in the healthy and failing heart. Heart Fail. Rev. 2000;5:221–238
  22. Khairallah M, Labarthe F, Bouchard B, Danialou G, Petrof BJ, Des Rosiers C. Profiling substrate fluxes in the isolated working mouse heart using 13C-labeled substrates: focusing on the origin and fate of pyruvate and citrate carbons. Am. J. Physiol.: Heart Circ. Physiol. 2004;286:H1461–H1470
  23. Kristensen SR. Mechanisms of cell damage and enzyme release. Dan. Med. Bull. 1994;41:423–433
  24. Krumenacker JS, Hanafy KA, Murad F. Regulation of nitric oxide and soluble guanylyl cyclase. Brain Res. Bull. 2004;62:505–515
  25. Krumenacker JS, Hyder SM, Murad F. Estradiol rapidly inhibits soluble guanylyl cyclase expression in rat uterus. Proc. Natl. Acad. Sci. U. S. A. 2001;98:717–722
  26. Lei B, Lionetti V, Young ME, Chandler MP, d'Agostino C, Kang E, et al. Paradoxical downregulation of the glucose oxidation pathway despite enhanced flux in severe heart failure. J. Mol. Cell. Cardiol. 2004;36:567–576
  27. Letellier T, Malgat M, Mazat JP. Control of oxidative phosphorylation in rat muscle mitochondria: implications for mitochondrial myopathies. Biochim. Biophys. Acta. 1993;1141:58–64
  28. Matsui T, Rosenzweig A. Convergent signal transduction pathways controlling cardiomyocyte survival and function: the role of PI 3-kinase and Akt. J. Mol. Cell. Cardiol. 2005;38:63–71
  29. Momose M, Iguchi N, Imamura K, Usui H, Ueda T, Miyamoto K, et al. Depressed myocardial fatty acid metabolism in patients with muscular dystrophy. Neuromuscul. Disord. 2001;11:464–469
  30. Naruse H, Miyagi J, Arii T, Ohyanagi M, Iwasaki T, Jinnai K. The relationship between clinical stage, prognosis and myocardial damage in patients with Duchenne-type muscular dystrophy: five-year follow-up study. Ann. Nucl. Med. 2004;18:203–208
  31. Neubauer S. The failing heart—An engine out of fuel. N. Engl. J. Med. 2007;356:1140–1151
  32. Perloff JK, Henze E, Schelbert HR. Alterations in regional myocardial metabolism, perfusion, and wall motion in Duchenne muscular dystrophy studied by radionuclide imaging. Circulation. 1984;69:33–42
  33. Petrof BJ. Molecular pathophysiology of myofiber injury in deficiencies of the dystrophin–glycoprotein complex. Am. J. Phys. Med. Rehabil. 2002;81:S162–S174
  34. Quinlan JG, Hahn HS, Wong BL, Lorenz JN, Wenisch AS, Levin LS. Evolution of the mdx mouse cardiomyopathy: physiological and morphological findings. Neuromuscul. Disord. 2004;14:491–496
  35. Quinlivan RM, Lewis P, Marsden P, Dundas R, Robb SA, Baker E, et al. Cardiac function, metabolism and perfusion in Duchenne and Becker muscular dystrophy. Neuromuscul. Disord. 1996;6:237–246
  36. Recchia FA. Role of nitric oxide in the regulation of substrate metabolism in heart failure. Heart Fail. Rev. 2002;7:141–148
  37. Rodriguez M, Cai WJ, Kostin S, Lucchesi BR, Schaper J. Ischemia depletes dystrophin and inhibits protein synthesis in the canine heart: mechanisms of myocardial ischemic injury. J. Mol. Cell. Cardiol. 2005;38:723–733
  38. Rohman MS, Emoto N, Takeshima Y, Yokoyama M, Matsuo M. Decreased mAKAP, ryanodine receptor, and SERCA2a gene expression in mdx hearts. Biochem. Biophys. Res. Commun. 2003;310:228–235
  39. Schonekess BO, Brindley PG, Lopaschuk GD. Calcium regulation of glycolysis, glucose oxidation, and fatty acid oxidation in the aerobic and ischemic heart. Can. J. Physiol. Pharmacol. 1995;73:1632–1640
  40. Stanley WC, Recchia FA, Lopaschuk GD. Myocardial substrate metabolism in the normal and failing heart. Physiol. Rev. 2005;85:1093–1129
  41. Taegtmeyer H, Golfman L, Sharma S, Razeghi P, van AM. Linking gene expression to function: metabolic flexibility in the normal and diseased heart. Ann. N. Y. Acad. Sci. 2004;1015:202–213
  42. van Bilsen M, Smeets PJ, Gilde AJ, van der Vusse GJ. Metabolic remodelling of the failing heart: the cardiac burn-out syndrome?. Cardiovasc. Res. 2004;61:218–226
  43. Vatta M, Stetson SJ, Perez-Verdia A, Entman ML, Noon GP, Torre-Amione G, et al. Molecular remodelling of dystrophin in patients with end-stage cardiomyopathies and reversal in patients on assistance-device therapy. Lancet. 2002;359:936–941
  44. Wehling-Henricks M, Jordan MC, Roos KP, Deng B, Tidball JG. Cardiomyopathy in dystrophin-deficient hearts is prevented by expression of a neuronal nitric oxide synthase transgene in the myocardium. Hum. Mol. Genet. 2005;14:1921–1933
  45. Wilding JR, Schneider JE, Sang AE, Davies KE, Neubauer S, Clarke K. Dystrophin- and MLP-deficient mouse hearts: marked differences in morphology and function, but similar accumulation of cytoskeletal proteins. FASEB J. 2005;19:79–81
  46. Williams IA, Allen DG. Intracellular calcium handling in ventricular myocytes from mdx mice. Am. J. Physiol.: Heart Circ. Physiol. 2007;292:H846–H855
  47. Woods RL. Cardioprotective functions of atrial natriuretic peptide and B-type natriuretic peptide: a brief review. Clin. Exp. Pharmacol. Physiol. 2004;31:791–794
  48. Yasuda S, Townsend D, Michele DE, Favre EG, Day SM, Metzger JM. Dystrophic heart failure blocked by membrane sealant poloxamer. Nature. 2005;436:1025–1029
  49. Young LH, Li J, Baron SJ, Russell RR. AMP-activated protein kinase: a key stress signaling pathway in the heart. Trends Cardiovasc. Med. 2005;15:110–118
  50. Young ME, Razeghi P, Cedars AM, Guthrie PH, Taegtmeyer H. Intrinsic diurnal variations in cardiac metabolism and contractile function. Circ. Res. 2001;89:1199–1208
  51. Zhang X, Recchia FA, Bernstein R, Xu X, Nasjletti A, Hintze TH. Kinin-mediated coronary nitric oxide production contributes to the therapeutic action of angiotensin-converting enzyme and neutral endopeptidase inhibitors and amlodipine in the treatment in heart failure. J. Pharmacol. Exp. Ther. 1999;288:742–751
  52. Zhu X, Wheeler MT, Hadhazy M, Lam MY, McNally EM. Cardiomyopathy is independent of skeletal muscle disease in muscular dystrophy. FASEB J. 2002;16:1096–1098

PII: S0022-2828(07)01054-1

doi: 10.1016/j.yjmcc.2007.05.015

Journal of Molecular and Cellular Cardiology
Volume 43, Issue 2 , Pages 119-129 , August 2007

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