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Targeting the Mitochondria in Cardiovascular Diseases

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Mitochondria and Their Role in Cardiovascular Disease

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Abstract

While progress achieved in mitochondrial research has been mainly used in the discovery of the pathogenesis of neuromuscular, cardiovascular, and other diseases, more specific studies are needed to determine the severity of heart mitochondrial defects (either primary or secondary to myocardial alterations) and its contribution to the pathophysiology of cardiovascular diseases. This new knowledge could be applied to identify specific mitochondrial-targeted drugs to be used not only in the heart failure syndrome but also to reverse, or at least to slow, potential changes in cardiac cell structure and function which occur in many other cardiovascular diseases as well as in the aging heart.

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References

  1. DiMauro S, Mancuso M, Naini A. Mitochondrial encephalomyopathies: therapeutic approach. Ann N Y Acad Sci. 2004;1011:232–45.

    Article  PubMed  CAS  Google Scholar 

  2. Pollitt RJ. Disorders of mitochondrial long-chain fatty acid oxidation. J Inherit Metab Dis. 1995;18(4):473–90.

    Article  PubMed  CAS  Google Scholar 

  3. Pierpont ME, Breningstall GN, Stanley CA, Singh A. Familial carnitine transporter defect: A treatable cause of cardiomyopathy in children. Am Heart J. 2000;139(2 Pt 3):S96–106.

    Article  PubMed  CAS  Google Scholar 

  4. Freisinger P, Horvath R, Macmillan C, Peters J, Jaksch M. Reversion of hypertrophic cardiomyopathy in a patient with deficiency of the mitochondrial copper binding protein Sco2: is there a potential effect of copper? J Inherit Metab Dis. 2004;27(1):67–79.

    Article  PubMed  CAS  Google Scholar 

  5. Shoffner JM, Wallace DC. Oxidative phosphorylation diseases and mitochondrial DNA mutations: diagnosis and treatment. Annu Rev Nutr. 1994;14:535–68.

    Article  PubMed  CAS  Google Scholar 

  6. Bersin RM, Stacpoole PW. Dichloroacetate as metabolic therapy for myocardial ischemia and failure. Am Heart J. 1997;134(5 Pt 1):841–55.

    Article  PubMed  CAS  Google Scholar 

  7. Fragasso G, Palloshi A, Bassanelli G, Steggerda R, Montano C, Margonato A. Heart disease and diabetes: from pathophysiology to therapeutic options. Ital Heart J. 2004;5 Suppl 2:4S–15.

    PubMed  Google Scholar 

  8. Taivassalo T, Matthews PM, De Stefano N, et al. Combined ­aerobic training and dichloroacetate improve exercise capacity and indices of aerobic metabolism in muscle cytochrome oxidase deficiency. Neurology. 1996;47(2):529–34.

    Article  PubMed  CAS  Google Scholar 

  9. Ferrari R, Guardigli G, Mele D, Percoco GF, Ceconi C, Curello S. Oxidative stress during myocardial ischaemia and heart failure. Curr Pharm Des. 2004;10(14):1699–711.

    Article  PubMed  CAS  Google Scholar 

  10. Cooper JM, Schapira AH. Friedreich’s Ataxia: disease mechanisms, antioxidant and Coenzyme Q10 therapy. Biofactors. 2003;18(1–4):163–71.

    Article  PubMed  CAS  Google Scholar 

  11. Santos DL, Moreno AJ, Leino RL, Froberg MK, Wallace KB. Carvedilol protects against doxorubicin-induced mitochondrial cardiomyopathy. Toxicol Appl Pharmacol. 2002;185(3):218–27.

    Article  PubMed  CAS  Google Scholar 

  12. Dai DF, Chen T, Wanagat J, et al. Age-dependent cardiomyopathy in mitochondrial mutator mice is attenuated by overexpression of catalase targeted to mitochondria. Aging Cell. 2010;9(4):536–44.

    Article  PubMed  CAS  Google Scholar 

  13. Tsutsui H, Kinugawa S, Matsushima S. Mitochondrial oxidative stress and dysfunction in myocardial remodelling. Cardiovasc Res. 2009;81(3):449–56.

    Article  PubMed  CAS  Google Scholar 

  14. Lerman-Sagie T, Rustin P, Lev D, et al. Dramatic improvement in mitochondrial cardiomyopathy following treatment with idebenone. J Inherit Metab Dis. 2001;24(1):28–34.

    Article  PubMed  CAS  Google Scholar 

  15. Sayed-Ahmed MM, Salman TM, Gaballah HE, Abou El-Naga SA, Nicolai R, Calvani M. Propionyl-L-carnitine as protector against adriamycin-induced cardiomyopathy. Pharmacol Res. 2001;43(6):513–20.

    Article  PubMed  CAS  Google Scholar 

  16. Shite J, Qin F, Mao W, Kawai H, Stevens SY, Liang C. Antioxidant vitamins attenuate oxidative stress and cardiac dysfunction in tachycardia-induced cardiomyopathy. J Am Coll Cardiol. 2001;38(6):1734–40.

    Article  PubMed  CAS  Google Scholar 

  17. Matsushima S, Ide T, Yamato M, et al. Overexpression of mitochondrial peroxiredoxin-3 prevents left ventricular remodeling and failure after myocardial infarction in mice. Circulation. 2006;113(14):1779–86.

    Article  PubMed  CAS  Google Scholar 

  18. Davidson SM. Endothelial mitochondria and heart disease. Cardiovasc Res. 2010;88(1):58–66.

    Article  PubMed  CAS  Google Scholar 

  19. Nojiri H, Shimizu T, Funakoshi M, et al. Oxidative stress causes heart failure with impaired mitochondrial respiration. J Biol Chem. 2006;281(44):33789–801.

    Article  PubMed  CAS  Google Scholar 

  20. Zhang H, Luo Y, Zhang W, et al. Endothelial-specific expression of mitochondrial thioredoxin improves endothelial cell function and reduces atherosclerotic lesions. Am J Pathol. 2007;170(3):1108–20.

    Article  PubMed  CAS  Google Scholar 

  21. Lipshultz SE, Rifai N, Dalton VM, et al. The effect of dexrazoxane on myocardial injury in doxorubicin-treated children with acute lymphoblastic leukemia. N Engl J Med. 2004;351(2):145–53.

    Article  PubMed  CAS  Google Scholar 

  22. Zhu SG, Kukreja RC, Das A, Chen Q, Lesnefsky EJ, Xi L. Dietary nitrate supplementation protects against Doxorubicin-induced cardiomyopathy by improving mitochondrial function. J Am Coll Cardiol. 2011;57(21):2181–9.

    Article  PubMed  CAS  Google Scholar 

  23. Zhang Y, El-Sikhry H, Chaudhary KR, et al. Overexpression of CYP2J2 provides protection against doxorubicin-induced cardiotoxicity. Am J Physiol Heart Circ Physiol. 2009;297(1):H37–46.

    Article  PubMed  CAS  Google Scholar 

  24. Geromel V, Darin N, Chretien D, et al. Coenzyme Q(10) and idebenone in the therapy of respiratory chain diseases: rationale and comparative benefits. Mol Genet Metab. 2002;77(1–2):21–30.

    Article  PubMed  CAS  Google Scholar 

  25. Hausse AO, Aggoun Y, Bonnet D, et al. Idebenone and reduced cardiac hypertrophy in Friedreich’s ataxia. Heart. 2002;87(4):346–9.

    Article  PubMed  CAS  Google Scholar 

  26. Rustin P, Munnich A, Rotig A. Quinone analogs prevent enzymes targeted in Friedreich ataxia from iron-induced injury in vitro. Biofactors. 1999;9(2–4):247–51.

    Article  PubMed  CAS  Google Scholar 

  27. Rustin P. The use of antioxidants in Friedreich’s ataxia treatment. Expert Opin Investig Drugs. 2003;12(4):569–75.

    Article  PubMed  CAS  Google Scholar 

  28. Bayot A, Santos R, Camadro JM, Rustin P. Friedreich’s ataxia: the vicious circle hypothesis revisited. BMC Med. 2011;9:112.

    Article  PubMed  CAS  Google Scholar 

  29. Ogasahara S, Yorifuji S, Nishikawa Y, et al. Improvement of abnormal pyruvate metabolism and cardiac conduction defect with coenzyme Q10 in Kearns-Sayre syndrome. Neurology. 1985;35(3):372–7.

    Article  PubMed  CAS  Google Scholar 

  30. Mortensen SA, Vadhanavikit S, Baandrup U, Folkers K. Long-term coenzyme Q10 therapy: a major advance in the management of resistant myocardial failure. Drugs Exp Clin Res. 1985;11(8): 581–93.

    PubMed  CAS  Google Scholar 

  31. Hargreaves IP. Ubiquinone: cholesterol’s reclusive cousin. Ann Clin Biochem. 2003;40(Pt 3):207–18.

    Article  PubMed  CAS  Google Scholar 

  32. Mortensen SA. Overview on coenzyme Q10 as adjunctive therapy in chronic heart failure. Rationale, design and end-points of “Q-symbio”–a multinational trial. Biofactors. 2003;18(1–4):79–89.

    Article  PubMed  CAS  Google Scholar 

  33. Littarru GP, Tiano L. Clinical aspects of coenzyme Q10: an update. Nutrition. 2010;26(3):250–4.

    Article  PubMed  CAS  Google Scholar 

  34. Chen Y, Saari JT, Kang YJ. Weak antioxidant defenses make the heart a target for damage in copper-deficient rats. Free Radic Biol Med. 1994;17(6):529–36.

    Article  PubMed  CAS  Google Scholar 

  35. Radi R, Turrens JF, Chang LY, Bush KM, Crapo JD, Freeman BA. Detection of catalase in rat heart mitochondria. J Biol Chem. 1991;266(32):22028–34.

    PubMed  CAS  Google Scholar 

  36. Antunes F, Han D, Cadenas E. Relative contributions of heart mitochondria glutathione peroxidase and catalase to H(2)O(2) detoxification in in vivo conditions. Free Radic Biol Med. 2002;33(9):1260–7.

    Article  PubMed  CAS  Google Scholar 

  37. Phung CD, Ezieme JA, Turrens JF. Hydrogen peroxide metabolism in skeletal muscle mitochondria. Arch Biochem Biophys. 1994;315(2):479–82.

    Article  PubMed  CAS  Google Scholar 

  38. Judge S, Judge A, Grune T, Leeuwenburgh C. Short-term CR decreases cardiac mitochondrial oxidant production but increases carbonyl content. Am J Physiol Regul Integr Comp Physiol. 2004;286(2):R254–9.

    Article  PubMed  CAS  Google Scholar 

  39. Turko IV, Murad F. Quantitative protein profiling in heart mitochondria from diabetic rats. J Biol Chem. 2003;278(37):35844–9.

    Article  PubMed  CAS  Google Scholar 

  40. Radi R, Bush KM, Freeman BA. The role of cytochrome c and mitochondrial catalase in hydroperoxide-induced heart mitochondrial lipid peroxidation. Arch Biochem Biophys. 1993;300(1): 409–15.

    Article  PubMed  CAS  Google Scholar 

  41. Zhou Z, Kang YJ. Cellular and subcellular localization of catalase in the heart of transgenic mice. J Histochem Cytochem. 2000;48(5):585–94.

    Article  PubMed  CAS  Google Scholar 

  42. Fernandez-Checa JC, Garcia-Ruiz C, Colell A, et al. Oxidative stress: role of mitochondria and protection by glutathione. Biofactors. 1998;8(1–2):7–11.

    Article  PubMed  CAS  Google Scholar 

  43. Vaage J, Antonelli M, Bufi M, et al. Exogenous reactive oxygen species deplete the isolated rat heart of antioxidants. Free Radic Biol Med. 1997;22(1–2):85–92.

    Article  PubMed  CAS  Google Scholar 

  44. Hasinoff BB, Schnabl KL, Marusak RA, Patel D, Huebner E. Dexrazoxane (ICRF-187) protects cardiac myocytes against doxorubicin by preventing damage to mitochondria. Cardiovasc Toxicol. 2003;3(2):89–99.

    Article  PubMed  CAS  Google Scholar 

  45. Kang YJ. The antioxidant function of metallothionein in the heart. Proc Soc Exp Biol Med. 1999;222(3):263–73.

    Article  PubMed  CAS  Google Scholar 

  46. Nath R, Kumar D, Li T, Singal PK. Metallothioneins, oxidative stress and the cardiovascular system. Toxicology. 2000;155(1–3):17–26.

    Article  PubMed  CAS  Google Scholar 

  47. Ali MM, Frei E, Straub J, Breuer A, Wiessler M. Induction of metallothionein by zinc protects from daunorubicin toxicity in rats. Toxicology. 2002;179(1–2):85–93.

    Article  PubMed  CAS  Google Scholar 

  48. Okuda M, Lee HC, Kumar C, Chance B. Comparison of the effect of a mitochondrial uncoupler, 2,4-dinitrophenol and adrenaline on oxygen radical production in the isolated perfused rat liver. Acta Physiol Scand. 1992;145(2):159–68.

    Article  PubMed  CAS  Google Scholar 

  49. Korshunov SS, Korkina OV, Ruuge EK, Skulachev VP, Starkov AA. Fatty acids as natural uncouplers preventing generation of O2.- and H2O2 by mitochondria in the resting state. FEBS Lett. 1998;435(2–3):215–8.

    Article  PubMed  CAS  Google Scholar 

  50. Casteilla L, Rigoulet M, Penicaud L. Mitochondrial ROS metabolism: modulation by uncoupling proteins. IUBMB Life. 2001;52(3–5):181–8.

    Article  PubMed  CAS  Google Scholar 

  51. Papa S, Skulachev VP. Reactive oxygen species, mitochondria, apoptosis and aging. Mol Cell Biochem. 1997;174(1–2):305–19.

    Article  PubMed  CAS  Google Scholar 

  52. Vidal-Puig AJ, Grujic D, Zhang CY, et al. Energy metabolism in uncoupling protein 3 gene knockout mice. J Biol Chem. 2000;275(21):16258–66.

    Article  PubMed  CAS  Google Scholar 

  53. Hoerter J, Gonzalez-Barroso MD, Couplan E, et al. Mitochondrial uncoupling protein 1 expressed in the heart of transgenic mice protects against ischemic-reperfusion damage. Circulation. 2004;110(5):528–33.

    Article  PubMed  CAS  Google Scholar 

  54. Teshima Y, Akao M, Jones SP, Marban E. Uncoupling protein-2 overexpression inhibits mitochondrial death pathway in cardiomyocytes. Circ Res. 2003;93(3):192–200.

    Article  PubMed  CAS  Google Scholar 

  55. Ungvari Z, Gupte SA, Recchia FA, Batkai S, Pacher P. Role of oxidative-nitrosative stress and downstream pathways in various forms of cardiomyopathy and heart failure. Curr Vasc Pharmacol. 2005;3(3):221–9.

    Article  PubMed  CAS  Google Scholar 

  56. Pacher P, Liaudet L, Mabley JG, Cziraki A, Hasko G, Szabo C. Beneficial effects of a novel ultrapotent poly(ADP-ribose) polymerase inhibitor in murine models of heart failure. Int J Mol Med. 2006;17(2):369–75.

    PubMed  CAS  Google Scholar 

  57. Castro P, Vukasovic JL, Chiong M, et al. Effects of carvedilol on oxidative stress and chronotropic response to exercise in patients with chronic heart failure. Eur J Heart Fail. 2005;7(6):1033–9.

    Article  PubMed  CAS  Google Scholar 

  58. Chin BS, Gibbs CR, Blann AD, Lip GY. Neither carvedilol nor bisoprolol in maximally tolerated doses has any specific advantage in lowering chronic heart failure oxidant stress: implications for beta-blocker selection. Clin Sci (Lond). 2003;105(4):507–12.

    Article  CAS  Google Scholar 

  59. Nakamura K, Kusano K, Nakamura Y, et al. Carvedilol decreases elevated oxidative stress in human failing myocardium. Circulation. 2002;105(24):2867–71.

    Article  PubMed  CAS  Google Scholar 

  60. Kono Y, Nakamura K, Kimura H, et al. Elevated levels of oxidative DNA damage in serum and myocardium of patients with heart failure. Circ J. 2006;70(8):1001–5.

    Article  PubMed  CAS  Google Scholar 

  61. Chin BS, Langford NJ, Nuttall SL, Gibbs CR, Blann AD, Lip GY. Anti-oxidative properties of beta-blockers and angiotensin-converting enzyme inhibitors in congestive heart failure. Eur J Heart Fail. 2003;5(2):171–4.

    Article  PubMed  CAS  Google Scholar 

  62. Bauersachs J, Widder JD. Endothelial dysfunction in heart failure. Pharmacol Rep. 2008;60(1):119–26.

    PubMed  CAS  Google Scholar 

  63. Bauersachs J, Schafer A. Endothelial dysfunction in heart failure: mechanisms and therapeutic approaches. Curr Vasc Pharmacol. 2004;2(2):115–24.

    Article  PubMed  CAS  Google Scholar 

  64. Saudubray JM, Martin D, de Lonlay P, et al. Recognition and management of fatty acid oxidation defects: a series of 107 patients. J Inherit Metab Dis. 1999;22(4):488–502.

    Article  PubMed  CAS  Google Scholar 

  65. Brown-Harrison MC, Nada MA, Sprecher H, et al. Very long chain acyl-CoA dehydrogenase deficiency: successful treatment of acute cardiomyopathy. Biochem Mol Med. 1996;58(1):59–65.

    Article  PubMed  CAS  Google Scholar 

  66. Wallhaus TR, Taylor M, DeGrado TR, et al. Myocardial free fatty acid and glucose use after carvedilol treatment in patients with congestive heart failure. Circulation. 2001;103(20):2441–6.

    Article  PubMed  CAS  Google Scholar 

  67. Rupp H, Zarain-Herzberg A, Maisch B. The use of partial fatty acid oxidation inhibitors for metabolic therapy of angina pectoris and heart failure. Herz. 2002;27(7):621–36.

    Article  PubMed  Google Scholar 

  68. Stanley WC. Partial fatty acid oxidation inhibitors for stable angina. Expert Opin Investig Drugs. 2002;11(5):615–29.

    Article  PubMed  CAS  Google Scholar 

  69. Zarain-Herzberg A, Rupp H. Transcriptional modulators targeted at fuel metabolism of hypertrophied heart. Am J Cardiol. 1999;83(12A):31H–7.

    Article  PubMed  CAS  Google Scholar 

  70. Schmidt-Schweda S, Holubarsch C. First clinical trial with etomoxir in patients with chronic congestive heart failure. Clin Sci (Lond). 2000;99(1):27–35.

    Article  CAS  Google Scholar 

  71. Pepine CJ, Wolff AA. A controlled trial with a novel anti-ischemic agent, ranolazine, in chronic stable angina pectoris that is responsive to conventional antianginal agents. Ranolazine Study Group. Am J Cardiol. 1999;84(1):46–50.

    Article  PubMed  CAS  Google Scholar 

  72. Fragasso G, Piatti Md PM, Monti L, et al. Short- and long-term beneficial effects of trimetazidine in patients with diabetes and ischemic cardiomyopathy. Am Heart J. 2003;146(5):E18.

    Article  PubMed  CAS  Google Scholar 

  73. Kantor PF, Lucien A, Kozak R, Lopaschuk GD. The antianginal drug trimetazidine shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3-ketoacyl coenzyme A thiolase. Circ Res. 2000;86(5):580–8.

    Article  PubMed  CAS  Google Scholar 

  74. MacInnes A, Fairman DA, Binding P, et al. The antianginal agent trimetazidine does not exert its functional benefit via inhibition of mitochondrial long-chain 3-ketoacyl coenzyme A thiolase. Circ Res. 2003;93(3):e26–32.

    Article  PubMed  CAS  Google Scholar 

  75. Tabbi-Anneni I, Helies-Toussaint C, Morin D, Bescond-Jacquet A, Lucien A, Grynberg A. Prevention of heart failure in rats by trimetazidine treatment: a consequence of accelerated phospholipid turnover? J Pharmacol Exp Ther. 2003;304(3):1003–9.

    Article  PubMed  CAS  Google Scholar 

  76. Chung MK. Vitamins, supplements, herbal medicines, and arrhythmias. Cardiol Rev. 2004;12(2):73–84.

    Article  PubMed  Google Scholar 

  77. Tavazzi L, Tognoni G, Franzosi MG, et al. Rationale and design of the GISSI heart failure trial: a large trial to assess the effects of n-3 polyunsaturated fatty acids and rosuvastatin in symptomatic congestive heart failure. Eur J Heart Fail. 2004;6(5):635–41.

    PubMed  CAS  Google Scholar 

  78. Singer P, Wirth M. Can n-3 PUFA reduce cardiac arrhythmias? Results of a clinical trial. Prostaglandins Leukot Essent Fatty Acids. 2004;71(3):153–9.

    Article  PubMed  CAS  Google Scholar 

  79. Pepe S, Tsuchiya N, Lakatta EG, Hansford RG. PUFA and aging modulate cardiac mitochondrial membrane lipid composition and Ca2+ activation of PDH. Am J Physiol. 1999;276(1 Pt 2):H149–58.

    PubMed  CAS  Google Scholar 

  80. Xu Z, Jiao Z, Cohen MV, Downey JM. Protection from AMP 579 can be added to that from either cariporide or ischemic preconditioning in ischemic rabbit heart. J Cardiovasc Pharmacol. 2002;40(4):510–8.

    Article  PubMed  CAS  Google Scholar 

  81. Inagaki K, Chen L, Ikeno F, et al. Inhibition of delta-protein kinase C protects against reperfusion injury of the ischemic heart in vivo. Circulation. 2003;108(19):2304–7.

    Article  PubMed  CAS  Google Scholar 

  82. Inoue K, Ando S, Itagaki T, Shiojiri Y, Kashima T, Takaba T. Intracellular calcium increasing at the beginning of reperfusion assists the early recovery of myocardial contractility after diltiazem cardioplegia. Jpn J Thorac Cardiovasc Surg. 2003;51(3):98–103.

    Article  PubMed  Google Scholar 

  83. Kroner A, Seitelberger R, Schirnhofer J, et al. Diltiazem during reperfusion preserves high energy phosphates by protection of mitochondrial integrity. Eur J Cardiothorac Surg. 2002;21(2):224–31.

    Article  PubMed  CAS  Google Scholar 

  84. Bertolet BD. Calcium antagonists in the post-myocardial infarction setting. Drugs Aging. 1999;15(6):461–70.

    Article  PubMed  CAS  Google Scholar 

  85. Theroux P, Gregoire J, Chin C, Pelletier G, de Guise P, Juneau M. Intravenous diltiazem in acute myocardial infarction. Diltiazem as adjunctive therapy to activase (DATA) trial. J Am Coll Cardiol. 1998;32(3):620–8.

    Article  PubMed  CAS  Google Scholar 

  86. Pizzetti G, Mailhac A, Li Volsi L, et al. Beneficial effects of diltiazem during myocardial reperfusion: a randomized trial in acute myocardial infarction. Ital Heart J. 2001;2(10):757–65.

    PubMed  CAS  Google Scholar 

  87. Matlib MA, McFarland KL. Diltiazem inhibition of sodium-induced calcium release. Effects on energy metabolism of heart mitochondria. Am J Hypertens. 1991;4(7 Pt 2):435S–41.

    PubMed  CAS  Google Scholar 

  88. Malhotra R, Mishra M, Kler TS, Kohli VM, Mehta Y, Trehan N. Cardioprotective effects of diltiazem infusion in the perioperative period. Eur J Cardiothorac Surg. 1997;12(3):420–7.

    Article  PubMed  CAS  Google Scholar 

  89. Leesar MA, Stoddard MF, Xuan YT, Tang XL, Bolli R. Nonelectrocardiographic evidence that both ischemic preconditioning and adenosine preconditioning exist in humans. J Am Coll Cardiol. 2003;42(3):437–45.

    Article  PubMed  CAS  Google Scholar 

  90. Crisafulli A, Melis F, Tocco F, et al. Exercise-induced and nitroglycerin-induced myocardial preconditioning improves hemodynamics in patients with angina. Am J Physiol Heart Circ Physiol. 2004;287(1):H235–42.

    Article  PubMed  CAS  Google Scholar 

  91. Argaud L, Ovize M. How to use the paradigm of ischemic preconditioning to protect the heart? Med Sci (Paris). 2004;20:521–5.

    Article  Google Scholar 

  92. de Ruijter W, Musters RJ, Boer C, Stienen GJ, Simonides WS, de Lange JJ. The cardioprotective effect of sevoflurane depends on protein kinase C activation, opening of mitochondrial K(+)(ATP) channels, and the production of reactive oxygen species. Anesth Analg. 2003;97(5):1370–6.

    Article  PubMed  CAS  Google Scholar 

  93. Zaugg M, Lucchinetti E, Spahn DR, Pasch T, Schaub MC. Volatile anesthetics mimic cardiac preconditioning by priming the activation of mitochondrial K(ATP) channels via multiple signaling pathways. Anesthesiology. 2002;97(1):4–14.

    Article  PubMed  CAS  Google Scholar 

  94. Stowe DF, Kevin LG. Cardiac preconditioning by volatile anesthetic agents: a defining role for altered mitochondrial bioenergetics. Antioxid Redox Signal. 2004;6(2):439–48.

    Article  PubMed  CAS  Google Scholar 

  95. Julier K, da Silva R, Garcia C, et al. Preconditioning by sevoflurane decreases biochemical markers for myocardial and renal dysfunction in coronary artery bypass graft surgery: a double-blinded, placebo-controlled, multicenter study. Anesthesiology. 2003;98(6):1315–27.

    Article  PubMed  CAS  Google Scholar 

  96. Dziegiel P, Podhorska-Okolow M, Surowiak P, Ciesielska U, Rabczynski J, Zabel M. Influence of exogenous melatonin on doxorubicin-evoked effects in myocardium and in transplantable Morris hepatoma in rats. In Vivo. 2003;17(4):325–8.

    PubMed  CAS  Google Scholar 

  97. Tanaka M, Nakae S, Terry RD, et al. Cardiomyocyte-specific Bcl-2 overexpression attenuates ischemia-reperfusion injury, immune response during acute rejection, and graft coronary artery disease. Blood. 2004;104(12):3789–96.

    Article  PubMed  CAS  Google Scholar 

  98. Halestrap AP, Clarke SJ, Javadov SA. Mitochondrial permeability transition pore opening during myocardial reperfusion–a target for cardioprotection. Cardiovasc Res. 2004;61(3):372–85.

    Article  PubMed  CAS  Google Scholar 

  99. Minners J, van den Bos EJ, Yellon DM, Schwalb H, Opie LH, Sack MN. Dinitrophenol, cyclosporin A, and trimetazidine modulate preconditioning in the isolated rat heart: support for a mitochondrial role in cardioprotection. Cardiovasc Res. 2000;47(1):68–73.

    Article  PubMed  CAS  Google Scholar 

  100. Ganote CE, Armstrong SC. Effects of CCCP-induced mitochondrial uncoupling and cyclosporin A on cell volume, cell injury and preconditioning protection of isolated rabbit cardiomyocytes. J Mol Cell Cardiol. 2003;35(7):749–59.

    Article  PubMed  CAS  Google Scholar 

  101. Holmuhamedov EL, Jahangir A, Oberlin A, Komarov A, Colombini M, Terzic A. Potassium channel openers are uncoupling protonophores: implication in cardioprotection. FEBS Lett. 2004;568(1–3):167–70.

    Article  PubMed  CAS  Google Scholar 

  102. Fischer UM, Tossios P, Huebner A, Geissler HJ, Bloch W, Mehlhorn U. Myocardial apoptosis prevention by radical scavenging in patients undergoing cardiac surgery. J Thorac Cardiovasc Surg. 2004;128(1):103–8.

    Article  PubMed  CAS  Google Scholar 

  103. Bagchi D, Sen CK, Ray SD, et al. Molecular mechanisms of cardioprotection by a novel grape seed proanthocyanidin extract. Mutat Res. 2003;523–524:87–97.

    PubMed  Google Scholar 

  104. Brookes PS, Digerness SB, Parks DA, Darley-Usmar V. Mitochondrial function in response to cardiac ischemia-reperfusion after oral treatment with quercetin. Free Radic Biol Med. 2002;32(11):1220–8.

    Article  PubMed  CAS  Google Scholar 

  105. Sato M, Maulik N, Das DK. Cardioprotection with alcohol: role of both alcohol and polyphenolic antioxidants. Ann N Y Acad Sci. 2002;957:122–35.

    Article  PubMed  CAS  Google Scholar 

  106. Olivencia-Yurvati AH, Blair JL, Baig M, Mallet RT. Pyruvate-enhanced cardioprotection during surgery with cardiopulmonary bypass. J Cardiothorac Vasc Anesth. 2003;17(6):715–20.

    Article  PubMed  Google Scholar 

  107. Flood A, Hack BD, Headrick JP. Pyruvate-dependent preconditioning and cardioprotection in murine myocardium. Clin Exp Pharmacol Physiol. 2003;30(3):145–52.

    Article  PubMed  CAS  Google Scholar 

  108. Suzuki YJ. Growth factor signaling for cardioprotection against oxidative stress-induced apoptosis. Antioxid Redox Signal. 2003;5(6):741–9.

    Article  PubMed  CAS  Google Scholar 

  109. Chao W, Matsui T, Novikov MS, et al. Strategic advantages of insulin-like growth factor-I expression for cardioprotection. J Gene Med. 2003;5(4):277–86.

    Article  PubMed  CAS  Google Scholar 

  110. Matsui T, Li L, Wu JC, et al. Phenotypic spectrum caused by transgenic overexpression of activated Akt in the heart. J Biol Chem. 2002;277(25):22896–901.

    Article  PubMed  CAS  Google Scholar 

  111. Latronico MV, Costinean S, Lavitrano ML, Peschle C, Condorelli G. Regulation of cell size and contractile function by AKT in cardiomyocytes. Ann N Y Acad Sci. 2004;1015:250–60.

    Article  PubMed  CAS  Google Scholar 

  112. Shiraishi I, Melendez J, Ahn Y, et al. Nuclear targeting of Akt enhances kinase activity and survival of cardiomyocytes. Circ Res. 2004;94(7):884–91.

    Article  PubMed  CAS  Google Scholar 

  113. Jonassen AK, Sack MN, Mjos OD, Yellon DM. Myocardial protection by insulin at reperfusion requires early administration and is mediated via Akt and p70s6 kinase cell-survival signaling. Circ Res. 2001;89(12):1191–8.

    Article  PubMed  CAS  Google Scholar 

  114. Sack MN, Yellon DM. Insulin therapy as an adjunct to reperfusion after acute coronary ischemia: a proposed direct myocardial cell survival effect independent of metabolic modulation. J Am Coll Cardiol. 2003;41(8):1404–7.

    Article  PubMed  CAS  Google Scholar 

  115. Larsson NG, Rustin P. Animal models for respiratory chain disease. Trends Mol Med. 2001;7(12):578–81.

    Article  PubMed  CAS  Google Scholar 

  116. Schuler AM, Wood PA. Mouse models for disorders of mitochondrial fatty acid beta-oxidation. ILAR J. 2002;43(2):57–65.

    PubMed  CAS  Google Scholar 

  117. Graham BH, Waymire KG, Cottrell B, Trounce IA, MacGregor GR, Wallace DC. A mouse model for mitochondrial myopathy and cardiomyopathy resulting from a deficiency in the heart/muscle isoform of the adenine nucleotide translocator. Nat Genet. 1997;16(3):226–34.

    Article  PubMed  CAS  Google Scholar 

  118. Lebovitz RM, Zhang H, Vogel H, et al. Neurodegeneration, myocardial injury, and perinatal death in mitochondrial superoxide dismutase-deficient mice. Proc Natl Acad Sci USA. 1996;93(18):9782–7.

    Article  PubMed  CAS  Google Scholar 

  119. Wang J, Wilhelmsson H, Graff C, et al. Dilated cardiomyopathy and atrioventricular conduction blocks induced by heart-specific inactivation of mitochondrial DNA gene expression. Nat Genet. 1999;21(1):133–7.

    Article  PubMed  CAS  Google Scholar 

  120. Puccio H, Simon D, Cossee M, et al. Mouse models for Friedreich ataxia exhibit cardiomyopathy, sensory nerve defect and Fe-S enzyme deficiency followed by intramitochondrial iron deposits. Nat Genet. 2001;27(2):181–6.

    Article  PubMed  CAS  Google Scholar 

  121. Kurtz DM, Rinaldo P, Rhead WJ, et al. Targeted disruption of mouse long-chain acyl-CoA dehydrogenase gene reveals crucial roles for fatty acid oxidation. Proc Natl Acad Sci USA. 1998;95(26):15592–7.

    Article  PubMed  CAS  Google Scholar 

  122. Ibdah JA, Paul H, Zhao Y, et al. Lack of mitochondrial trifunctional protein in mice causes neonatal hypoglycemia and sudden death. J Clin Invest. 2001;107(11):1403–9.

    Article  PubMed  CAS  Google Scholar 

  123. Exil VJ, Roberts RL, Sims H, et al. Very-long-chain acyl-coenzyme a dehydrogenase deficiency in mice. Circ Res. 2003;93(5):448–55.

    Article  PubMed  CAS  Google Scholar 

  124. Ruiz-Lozano P, Smith SM, Perkins G, et al. Energy deprivation and a deficiency in downstream metabolic target genes during the onset of embryonic heart failure in RXRalpha−/− embryos. Development. 1998;125(3):533–44.

    PubMed  CAS  Google Scholar 

  125. Naya FJ, Black BL, Wu H, et al. Mitochondrial deficiency and cardiac sudden death in mice lacking the MEF2A transcription factor. Nat Med. 2002;8(11):1303–9.

    Article  PubMed  CAS  Google Scholar 

  126. Sligh JE, Levy SE, Waymire KG, et al. Maternal germ-line transmission of mutant mtDNAs from embryonic stem cell-derived chimeric mice. Proc Natl Acad Sci USA. 2000;97(26):14461–6.

    Article  PubMed  CAS  Google Scholar 

  127. Inoue K, Nakada K, Ogura A, et al. Generation of mice with ­mitochondrial dysfunction by introducing mouse mtDNA carrying a deletion into zygotes. Nat Genet. 2000;26(2):176–81.

    Article  PubMed  CAS  Google Scholar 

  128. Guy J, Qi X, Pallotti F, et al. Rescue of a mitochondrial deficiency causing Leber Hereditary Optic Neuropathy. Ann Neurol. 2002;52(5):534–42.

    Article  PubMed  CAS  Google Scholar 

  129. Manfredi G, Fu J, Ojaimi J, et al. Rescue of a deficiency in ATP synthesis by transfer of MTATP6, a mitochondrial DNA-encoded gene, to the nucleus. Nat Genet. 2002;30(4):394–9.

    Article  PubMed  CAS  Google Scholar 

  130. Oca-Cossio J, Kenyon L, Hao H, Moraes CT. Limitations of allotopic expression of mitochondrial genes in mammalian cells. Genetics. 2003;165(2):707–20.

    PubMed  CAS  Google Scholar 

  131. Chinnery PF. New approaches to the treatment of mitochondrial disorders. Reprod Biomed Online. 2004;8(1):16–23.

    Article  PubMed  CAS  Google Scholar 

  132. Jenuth JP, Peterson AC, Shoubridge EA. Tissue-specific selection for different mtDNA genotypes in heteroplasmic mice. Nat Genet. 1997;16(1):93–5.

    Article  PubMed  CAS  Google Scholar 

  133. Meirelles FV, Smith LC. Mitochondrial genotype segregation in a mouse heteroplasmic lineage produced by embryonic karyoplast transplantation. Genetics. 1997;145(2):445–51.

    PubMed  CAS  Google Scholar 

  134. Pinkert CA, Trounce IA. Production of transmitochondrial mice. Methods. 2002;26(4):348–57.

    Article  PubMed  CAS  Google Scholar 

  135. Levy SE, Waymire KG, Kim YL, MacGregor GR, Wallace DC. Transfer of chloramphenicol-resistant mitochondrial DNA into the chimeric mouse. Transgenic Res. 1999;8(2):137–45.

    Article  PubMed  CAS  Google Scholar 

  136. McKenzie M, Trounce IA, Cassar CA, Pinkert CA. Production of homoplasmic xenomitochondrial mice. Proc Natl Acad Sci USA. 2004;101(6):1685–90.

    Article  PubMed  CAS  Google Scholar 

  137. Barritt JA, Brenner CA, Malter HE, Cohen J. Mitochondria in human offspring derived from ooplasmic transplantation. Hum Reprod. 2001;16(3):513–6.

    Article  PubMed  CAS  Google Scholar 

  138. Malter HE, Cohen J. Ooplasmic transfer: animal models assist human studies. Reprod Biomed Online. 2002;5(1):26–35.

    Article  PubMed  Google Scholar 

  139. Hawes SM, Sapienza C, Latham KE. Ooplasmic donation in humans: the potential for epigenic modifications. Hum Reprod. 2002;17(4):850–2.

    Article  PubMed  Google Scholar 

  140. St John JC. Ooplasm donation in humans: the need to investigate the transmission of mitochondrial DNA following cytoplasmic transfer. Hum Reprod. 2002;17(8):1954–8.

    Article  PubMed  Google Scholar 

  141. Poulton J, Marchington DR. Segregation of mitochondrial DNA (mtDNA) in human oocytes and in animal models of mtDNA disease: clinical implications. Reproduction. 2002;123(6):751–5.

    Article  PubMed  CAS  Google Scholar 

  142. Maron BJ, Moller JH, Seidman CE, et al. Impact of laboratory molecular diagnosis on contemporary diagnostic criteria for genetically transmitted cardiovascular diseases: hypertrophic cardiomyopathy, long-QT syndrome, and marfan syndrome: A statement for healthcare professionals from the councils on clinical cardiology, cardiovascular disease in the young, and basic science, american heart association. Circulation. 1998;98(14):1460–71.

    Article  CAS  Google Scholar 

  143. Marin-Garcia J, Goldenthal MJ. Understanding the impact of mitochondrial defects in cardiovascular disease: a review. J Card Fail. 2002;8(5):347–61.

    Article  PubMed  CAS  Google Scholar 

  144. van Den Bosch BJ, de Coo RF, Scholte HR, et al. Mutation analysis of the entire mitochondrial genome using denaturing high performance liquid chromatography. Nucleic Acids Res. 2000;28(20):E89.

    Article  Google Scholar 

  145. Marian AJ. Modifier genes for hypertrophic cardiomyopathy. Curr Opin Cardiol. 2002;17(3):242–52.

    Article  PubMed  CAS  Google Scholar 

  146. Carelli V, Giordano C, D’Amati G. Pathogenic expression of homoplasmic mtDNA mutations needs a complex nuclear-mitochondrial interaction. Trends Genet. 2003;19(5):257–62.

    Article  PubMed  CAS  Google Scholar 

  147. Dzau VJ. Predicting the future of human gene therapy for cardiovascular diseases: what will the management of coronary artery disease be like in 2005 and 2010? Am J Cardiol. 2003;92(9B):32N–5.

    Article  PubMed  Google Scholar 

  148. Baumgartner I, Isner JM. Somatic gene therapy in the cardiovascular system. Annu Rev Physiol. 2001;63:427–50.

    Article  PubMed  CAS  Google Scholar 

  149. Pislaru S, Janssens SP, Gersh BJ, Simari RD. Defining gene ­transfer before expecting gene therapy: putting the horse before the cart. Circulation. 2002;106(5):631–6.

    Article  PubMed  CAS  Google Scholar 

  150. Isner JM, Vale PR, Symes JF, Losordo DW. Assessment of risks associated with cardiovascular gene therapy in human subjects. Circ Res. 2001;89(5):389–400.

    Article  PubMed  CAS  Google Scholar 

  151. Morishita R, Higaki J, Tomita N, Ogihara T. Application of transcription factor “decoy” strategy as means of gene therapy and study of gene expression in cardiovascular disease. Circ Res. 1998;82(10):1023–8.

    Article  PubMed  CAS  Google Scholar 

  152. Chaudhri BB, del Monte F, Harding SE, Hajjar RJ. Gene transfer in cardiac myocytes. Surg Clin North Am. 2004;84(1):141–59. ix–x.

    Article  PubMed  Google Scholar 

  153. Melo LG, Agrawal R, Zhang L, et al. Gene therapy strategy for long-term myocardial protection using adeno-associated virus-mediated delivery of heme oxygenase gene. Circulation. 2002;105(5):602–7.

    Article  PubMed  CAS  Google Scholar 

  154. Abunasra HJ, Smolenski RT, Morrison K, et al. Efficacy of ­adenoviral gene transfer with manganese superoxide dismutase and endothelial nitric oxide synthase in reducing ischemia and reperfusion injury. Eur J Cardiothorac Surg. 2001;20(1): 153–8.

    Article  PubMed  CAS  Google Scholar 

  155. Jayakumar J, Suzuki K, Sammut IA, et al. Heat shock protein 70 gene transfection protects mitochondrial and ventricular function against ischemia-reperfusion injury. Circulation. 2001;104(12 Suppl 1):I303–7.

    PubMed  CAS  Google Scholar 

  156. Chatterjee S, Stewart AS, Bish LT, et al. Viral gene transfer of the antiapoptotic factor Bcl-2 protects against chronic postischemic heart failure. Circulation. 2002;106(12 Suppl 1):I212–7.

    PubMed  Google Scholar 

  157. Weisleder N, Taffet GE, Capetanaki Y. Bcl-2 overexpression ­corrects mitochondrial defects and ameliorates inherited desmin null cardiomyopathy. Proc Natl Acad Sci USA. 2004;101(3): 769–74.

    Article  PubMed  CAS  Google Scholar 

  158. Stacpoole PW, Owen R, Flotte TR. The pyruvate dehydrogenase complex as a target for gene therapy. Curr Gene Ther. 2003;3(3):239–45.

    Article  PubMed  CAS  Google Scholar 

  159. McGregor A, Temperley R, Chrzanowska-Lightowlers ZM, Lightowlers RN. Absence of expression from RNA internalised into electroporated mammalian mitochondria. Mol Genet Genomics. 2001;265(4):721–9.

    Article  PubMed  CAS  Google Scholar 

  160. Turnbull DM, Lightowlers RN. A roundabout route to gene therapy. Nat Genet. 2002;30(4):345–6.

    Article  PubMed  CAS  Google Scholar 

  161. Tanaka M, Borgeld HJ, Zhang J, et al. Gene therapy for mitochondrial disease by delivering restriction endonuclease SmaI into mitochondria. J Biomed Sci. 2002;9(6 Pt 1):534–41.

    PubMed  CAS  Google Scholar 

  162. Ojaimi J, Pan J, Santra S, Snell WJ, Schon EA. An algal nucleus-encoded subunit of mitochondrial ATP synthase rescues a defect in the analogous human mitochondrial-encoded subunit. Mol Biol Cell. 2002;13(11):3836–44.

    Article  PubMed  CAS  Google Scholar 

  163. Manfredi G, Gupta N, Vazquez-Memije ME, et al. Oligomycin induces a decrease in the cellular content of a pathogenic mutation in the human mitochondrial ATPase 6 gene. J Biol Chem. 1999;274(14):9386–91.

    Article  PubMed  CAS  Google Scholar 

  164. Fu K, Hartlen R, Johns T, Genge A, Karpati G, Shoubridge EA. A novel heteroplasmic tRNAleu(CUN) mtDNA point mutation in a sporadic patient with mitochondrial encephalomyopathy segregates rapidly in skeletal muscle and suggests an approach to therapy. Hum Mol Genet. 1996;5(11):1835–40.

    Article  PubMed  CAS  Google Scholar 

  165. Clark KM, Bindoff LA, Lightowlers RN, et al. Reversal of a mitochondrial DNA defect in human skeletal muscle. Nat Genet. 1997;16(3):222–4.

    Article  PubMed  CAS  Google Scholar 

  166. Taivassalo T, Fu K, Johns T, Arnold D, Karpati G, Shoubridge EA. Gene shifting: a novel therapy for mitochondrial myopathy. Hum Mol Genet. 1999;8(6):1047–52.

    Article  PubMed  CAS  Google Scholar 

  167. Chinnery PF, Taylor RW, Diekert K, Lill R, Turnbull DM, Lightowlers RN. Peptide nucleic acid delivery to human mitochondria. Gene Ther. 1999;6(12):1919–28.

    Article  PubMed  CAS  Google Scholar 

  168. Taylor RW, Chinnery PF, Turnbull DM, Lightowlers RN. Selective inhibition of mutant human mitochondrial DNA replication in vitro by peptide nucleic acids. Nat Genet. 1997;15(2):212–5.

    Article  PubMed  CAS  Google Scholar 

  169. Muratovska A, Lightowlers RN, Taylor RW, et al. Targeting peptide nucleic acid (PNA) oligomers to mitochondria within cells by conjugation to lipophilic cations: implications for mitochondrial DNA replication, expression and disease. Nucleic Acids Res. 2001;29(9):1852–63.

    Article  PubMed  CAS  Google Scholar 

  170. Geromel V, Cao A, Briane D, et al. Mitochondria transfection by oligonucleotides containing a signal peptide and vectorized by cationic liposomes. Antisense Nucleic Acid Drug Dev. 2001;11(3):175–80.

    Article  PubMed  CAS  Google Scholar 

  171. Flierl A, Jackson C, Cottrell B, Murdock D, Seibel P, Wallace DC. Targeted delivery of DNA to the mitochondrial compartment via import sequence-conjugated peptide nucleic acid. Mol Ther. 2003;7(4):550–7.

    Article  PubMed  CAS  Google Scholar 

  172. Weissig V, Lasch J, Erdos G, Meyer HW, Rowe TC, Hughes J. DQAsomes: a novel potential drug and gene delivery system made from Dequalinium. Pharm Res. 1998;15(2):334–7.

    Article  PubMed  CAS  Google Scholar 

  173. D’Souza GG, Rammohan R, Cheng SM, Torchilin VP, Weissig V. DQAsome-mediated delivery of plasmid DNA toward mitochondria in living cells. J Control Release. 2003;92(1–2):189–97.

    Article  PubMed  CAS  Google Scholar 

  174. Weissig V, Cheng SM, D’Souza GG. Mitochondrial pharmaceutics. Mitochondrion. 2004;3(4):229–44.

    Article  PubMed  CAS  Google Scholar 

  175. Lee M, Choi JS, Ko KS. Mitochondria targeting delivery of nucleic acids. Expert Opin Drug Deliv. 2008;5(8):879–87.

    Article  PubMed  CAS  Google Scholar 

  176. Kelso GF, Porteous CM, Coulter CV, et al. Selective targeting of a redox-active ubiquinone to mitochondria within cells: antioxidant and antiapoptotic properties. J Biol Chem. 2001;276(7):4588–96.

    Article  PubMed  CAS  Google Scholar 

  177. Smith RA, Porteous CM, Gane AM, Murphy MP. Delivery of bioactive molecules to mitochondria in vivo. Proc Natl Acad Sci USA. 2003;100(9):5407–12.

    Article  PubMed  CAS  Google Scholar 

  178. Zhao K, Zhao GM, Wu D, et al. Cell-permeable peptide antioxidants targeted to inner mitochondrial membrane inhibit mitochondrial swelling, oxidative cell death, and reperfusion injury. J Biol Chem. 2004;279(33):34682–90.

    Article  PubMed  CAS  Google Scholar 

  179. Lin TK, Hughes G, Muratovska A, et al. Specific modification of mitochondrial protein thiols in response to oxidative stress: a proteomics approach. J Biol Chem. 2002;277(19):17048–56.

    Article  PubMed  CAS  Google Scholar 

  180. Zullo SJ. Gene therapy of mitochondrial DNA mutations: a brief, biased history of allotopic expression in mammalian cells. Semin Neurol. 2001;21(3):327–35.

    Article  PubMed  CAS  Google Scholar 

  181. Menasche P. Skeletal myoblast transplantation for cardiac repair. Expert Rev Cardiovasc Ther. 2004;2(1):21–8.

    Article  PubMed  Google Scholar 

  182. Ito H, Taniyama Y, Iwakura K, et al. Intravenous nicorandil can preserve microvascular integrity and myocardial viability in patients with reperfused anterior wall myocardial infarction. J Am Coll Cardiol. 1999;33(3):654–60.

    Article  PubMed  CAS  Google Scholar 

  183. Rustin P, von Kleist-Retzow JC, Chantrel-Groussard K, Sidi D, Munnich A, Rotig A. Effect of idebenone on cardiomyopathy in Friedreich’s ataxia: a preliminary study. Lancet. 1999;354: 477–9.

    Article  PubMed  CAS  Google Scholar 

  184. Ennis IL, Li RA, Murphy AM, Marban E, Nuss HB. Dual gene therapy with SERCA1 and Kir2.1 abbreviates excitation without suppressing contractility. J Clin Invest. 2002;109:393–400.

    PubMed  CAS  Google Scholar 

  185. Beltrami AP, Barlucchi L, Torella D, et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell. 2003;114:763–76.

    Article  PubMed  CAS  Google Scholar 

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    José Marín-García M.D.

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Marín-García, J. (2013). Targeting the Mitochondria in Cardiovascular Diseases. In: Mitochondria and Their Role in Cardiovascular Disease. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-4599-9_23

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