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Deregulation of Mitochondrial Function: A Potential Common Theme for Cardiovascular Disease Development

  • Chapter
Oxidative Stress in Aging

Part of the book series: Aging Medicine ((AGME))

Summary

The pathogenesis of atherosclerosis has been intensively studied and described; yet, despite these advances, the underlying events that initiate athero-genesis are not yet fully understood. Consequently, cardiovascular disease remains the major cause of death and morbidity in the western world. Although studies are in general agreement that atherosclerosis is a chronic, inflammatory disease, and additionally, that increased oxidative stress plays a key factor in the early stages of disease development, the impact of such changes on the subcellular or organellar components and their functions that are relevant to cardiovascular disease inception are less appreciated. In this regard, studies are beginning to show that mitochondria are common targets of oxidative stress and that they may play significant roles in the regulation of cardiovascular cell function. A common theme among cardiovascular disease risk factors is that they can mediate mitochondrial damage and dysfunction, and moreover, that mitochondrial damage can significantly increase the risk for disease onset. Moreover, it has been recently suggested that the balance between mitochondrial energy efficiency, oxidant production, and thermogenesis that developed during human prehistory has long-term implications for human disease development, susceptibility, and evolution of disease. Hence, the emphasis of this review is discussion of the unique features of mitochondrial functional biology that potentially make it a central focal point in terms of the mechanistic basis of cardiovascular disease.

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References

  1. American Heart Association. Heart Disease and Stroke Statistics-2006 Update. Circulation 2006; 105:1–67.

    Google Scholar 

  2. Yang Z, Knight CA, Mamerow M, Vickers K, Penn A, Postlethwait E et al. Prenatal environmental tobacco smoke exposure promotes adult atherogenesis and mitochondrial damage in apoE−/− mice fed a chow diet. Circulation 110, 3715–3720. 2004.

    Google Scholar 

  3. Napoli C, De Nigris F, Welch JS et al. Maternal hypercholesterolemia during pregnancy promotes early atherogenesis in LDL receptor-deficient mice and alters aortic gene expression determined by microarray. Circulation 2002; 105(11):1360–1367.

    PubMed  CAS  Google Scholar 

  4. Ignarro LJ, Cirino G, Casini A, Napoli C. Nitric oxide as a signaling molecule in the vascular system: an overview. J Cardiovasc Pharmacol 1999; 34(6):879–886.

    PubMed  CAS  Google Scholar 

  5. Napoli C, D'Armiento FP, Mancini FP et al. Fatty streak formation occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia: intimal accumulation of low density lipoprotein and its oxidation precede monocyte recruitment into early atherosclerotic lesions. J Clin Invest 1997; 100(11):2680–2690.

    PubMed  CAS  Google Scholar 

  6. Napoli C, Glass CK, Witztum JL, Deutsch R, D'Armiento FP, Palinski W. Influence of maternal hypercholesterolaemia during pregnancy on progression of early atherosclerotic lesions in childhood: fate of early lesions in children (FELIC) study. Lancet 1999; 354(9186):1234–1241.

    PubMed  CAS  Google Scholar 

  7. Napoli C, Palinski W. Maternal hypercholesterolemia during pregnancy influences the later development of atherosclerosis: clinical and pathogenic implications. Eur Heart J 2001; 22(1):4–9.

    PubMed  CAS  Google Scholar 

  8. Palinski W, Napoli C. The fetal origins of atherosclerosis: maternal hypercholesterolemia, and cholesterol-lowering or antioxidant treatment during pregnancy influence in utero programming and postnatal susceptibility to atherogenesis. FASEB J 2002; 16(11):1348–1360.

    PubMed  CAS  Google Scholar 

  9. Oral H, Sivasubramanian N, Dyke DB, Mehta RH, Grossman PM, Briesmiester K et al. Myocardial proinflammatory cytokine expression and left ventricular remodeling in patients with chronic mitral regurgitation. Circulation 2003; 107(6):831–837.

    PubMed  Google Scholar 

  10. Tutar E, Kapadia SR, Ziada KM, Hobbs RE, L'Allier PL, Rincon G et al. Coronary atherosclerosis begins at young age: intravascular ultrasound evidence of disease in individuals <20 years old. Circulation 1999; 100(18):524.

    Google Scholar 

  11. Tuzcu EM, Kapadia SR, Tutar E et al. High prevalence of coronary atherosclerosis in asymptomatic teenagers and young adults: evidence from intravascular ultrasound. Circulation 2001; 103(22):2705–2710.

    PubMed  CAS  Google Scholar 

  12. Dollery CM, Libby P. Atherosclerosis and proteinase activation. Cardiovasc Rese 2006; 69(3):625–635.

    CAS  Google Scholar 

  13. Libby P, Theroux P. Pathophysiology of coronary artery disease. Circulation 2005; 111(25):3481–3488.

    PubMed  Google Scholar 

  14. Libby P. Inflammation and cardiovascular disease mechanisms. Am J Clin Nutr 2006; 83(2):456S–460S.

    PubMed  CAS  Google Scholar 

  15. Libby P. Inflammatory components of the atherosclerotic plaque. Atheroscler Suppl 2006; 7(3):168.

    Google Scholar 

  16. Glagov S, Vito R, Giddens DP, Zarins CK. Microarchitecture and composition of artery walls: relationship to location, diameter and the distribution of mechanical-stress. J Hypertens 1992; 10:S101–S104.

    CAS  Google Scholar 

  17. Glagov S. Intimal hyperplasia, vascular modeling, and the restenosis problem. Circulation 1994; 89(6):2888–2891.

    PubMed  CAS  Google Scholar 

  18. Glagov S, Bassiouny HS, Giddens DP, Zarins CK. Pathobiology of plaque modeling and complication. Surg Clin North Am 1995; 75(4):545–556.

    PubMed  CAS  Google Scholar 

  19. Glagov S, Bassiouny HS, Sakaguchi Y, Goudet CA, Vito RP. Mechanical determinants of plaque modeling, remodeling and disruption. Atherosclerosis 1997; 131:S13–S14.

    PubMed  CAS  Google Scholar 

  20. Glagov S, Weisenberg E, Zarins C, Stankunavicius R, Kolletis G. Compensatory enlargement of human atherosclerotic coronary arteries. N Engl J Med 1987; 316:371–375.

    Google Scholar 

  21. Hackett D, Davies G, Maseri A. Pre-existing coronary stenosis in patients with first myocar-dial infarction are not necessarily severe. Eur Heart J 1988; 9:1317–1323.

    PubMed  CAS  Google Scholar 

  22. Rioufol G, Finet G, Andre-Fouet X et al. Multiple atherosclerotic plaque rupture in acute coronary syndromes. Arch Mal Coeur Vaiss 2002; 95(3):157–165.

    PubMed  CAS  Google Scholar 

  23. Rioufol G, Finet G, Ginon I et al. Multiple atherosclerotic plaque rupture in acute coronary syndrome: a three-vessel intravascular ultrasound study. Circulation 2002; 106(7):804–808.

    PubMed  CAS  Google Scholar 

  24. Rioufol G, Gilard M, Finet G. Upstream or downstream longitudinal patterns of ruptured coronary plaques by IVUS. Eur Heart J 2005; 26:715.

    Google Scholar 

  25. Schoenhagen P, Stone GW, Nissen SE et al. Coronary plaque morphology and frequency of ulceration distant from culprit lesions in patients with unstable and stable presentation. Arterioscler Thromb Vasc Biol 2003; 23(10):1895–1900.

    PubMed  CAS  Google Scholar 

  26. Kotani J, Mintz GS, Castagna MT, Pinnow E, Berzingi CO, Bui AB et al. Intravascular ultrasound analysis of infarct-related and non-infarct-related arteries in patients who presented with an acute myocardial infarction. Circulation 2003; 107(23):2889–2893.

    PubMed  Google Scholar 

  27. Hong MK, Mintz GS, Lee CW et al. Comparison of coronary plaque rupture between stable angina and acute myocardial infarction: a three-vessel intravascular ultrasound study in 235 patients. Circulation 2004; 110(8):928–933.

    PubMed  Google Scholar 

  28. Tanaka A, Shimada K, Sano T et al. Multiple plaque rupture and c-reactive protein in acute myocardial infarction. J Am Coll Cardiol 2005; 45(10):1594–1599.

    PubMed  CAS  Google Scholar 

  29. Carpenter KL, Taylor SE, van der Veen C, Mitchinson MJ. Evidence of lipid oxidation in pulmonary artery atherosclerosis. Atherosclerosis 1995; 118:169–172.

    PubMed  CAS  Google Scholar 

  30. Halliwell B. Free radicals, reactive oxygen species and human disease: a critical evaluation with special reference to atherosclerosis. Br J Exp Pathol 1989; 70:737–757.

    PubMed  CAS  Google Scholar 

  31. Berliner JA, Heinecke JW. The role of oxidized lipoproteins in atherogenesis. Free Radic Biol Med 1996; 20:707–727.

    PubMed  CAS  Google Scholar 

  32. Massaeli H, Pierce GN. Involvement of lipoproteins, free radicals, and calcium in cardiovascular disease processes. Cardiovasc Res 1995; 29:597–603.

    PubMed  CAS  Google Scholar 

  33. Freeman BA, White CR, Gutierrez H, Paler-Martinez A, Tarpey MM, Rubbo H. Oxygen radical-nitric oxide reactions in vascular diseases. Adv Pharmacol 1995; 34:45–69.

    PubMed  CAS  Google Scholar 

  34. Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL. Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med 1989; 321:1196–1197.

    Google Scholar 

  35. Witztum JL, Steinberg D. Role of oxidized low density lipoprotein in atherogenesis. J Clin Invest 1991; 88:1785–1792.

    PubMed  CAS  Google Scholar 

  36. Reid V, Mitchinson MJ, Skepper J. Cytotoxicity of oxidised low density lipoprotein to mouse peritoneal macrophages: an ultrastructural study. J Pathol 1993; 171:321–328.

    PubMed  CAS  Google Scholar 

  37. Holland JA, Ziegler LM, Meyer JW. Atherogenic levels of low-density lipoprotein increase hydrogen peroxide generation in cultured human endothelial cells: Possible mechanism of heightened endocytosis. J Cell Physiol 1996; 166:144–151.

    PubMed  CAS  Google Scholar 

  38. Ohara Y, Peterson TE, Harrison DG. Hypercholesterolemia increases endothelial superoxide anion production. J Clin Invest 1993; 91:2546–2551.

    PubMed  CAS  Google Scholar 

  39. Diaz MN, Frei B, Vita JA, Keaney JF. Mechanisms of disease: antioxidants and atherosclerotic heart disease. N Engl J Med 1997; 337(6):408–416.

    PubMed  CAS  Google Scholar 

  40. Cai H, Harrison DG. Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res 2000; 87(10):840–844.

    PubMed  CAS  Google Scholar 

  41. Harrison D, Griendling KK, Landmesser U, Hornig B, Drexler H. Role of oxidative stress in atherosclerosis. Am J Cardiol 2003; 91(3):7A–11A.

    PubMed  CAS  Google Scholar 

  42. Dhalla NS, Temsah RM, Netticadan T. Role of oxidative stress in cardiovascular diseases. J Hypertens 2000; 18(6):655–673.

    PubMed  CAS  Google Scholar 

  43. Iuliano L. The oxidant stress hypothesis of atherogenesis. Lipids 2001; 36:S41–S44.

    PubMed  CAS  Google Scholar 

  44. Keith M, Geranmayegan A, Sole MJ, Kurian R et al. Increased oxidative stress in patients with congestive heart failure. J Am Coll Cardiol 1998; 31:1352–1356.

    PubMed  CAS  Google Scholar 

  45. Holvoet P, Perez G, Zhao Z, Brouwers E, Bernar H, Collen A. Malondialdehyde-modified low density lipoproteins in patients with atherosclerotic disease. J Clin Invest 1995; 95:2611–2619.

    PubMed  CAS  Google Scholar 

  46. Schmidt AM, Hori O, Chen JX, Li JF, Crandall J, Zhang J et al. Advanced glycation end-products interacting with their endothelial receptor induce expression of vascular cell adhesion molecule-1 (VCAM-1) in cultured human endothelial cells and mice. A potential mechanism for the accelerated vasculopathy of diabetes. J Clin Invest 1995; 96:1395–1403.

    PubMed  CAS  Google Scholar 

  47. Hazen SL, Heinecke JW. 3-chlorotyrosine, a specific marker of myeloperosidase-catalyzed oxidation, is markedly elevated in low density lipoprotein isolated from human atherosclerotic intima. J Clin Invest 1997; 99:2075–2081.

    PubMed  CAS  Google Scholar 

  48. Radi R, Rodriguez M, Castro L, Telleri R. Inhibition of mitochondrial electron transport by peroxynitrite. Arch Biochem Biophys 1994; 308:89–95.

    PubMed  CAS  Google Scholar 

  49. Radi R, Denicola A, Freeman BA. Peroxynitrite reactions with carbon dioxide-bicarbonate. Methods Enzymol 1999; 301:353–367.

    PubMed  CAS  Google Scholar 

  50. Ischiropoulos H. Biological tyrosine nitration: a pathophysiological function of nitric oxide and reactive oxygen species. Arch Biochem Biophys 1998; 356:1–11.

    PubMed  CAS  Google Scholar 

  51. Minetti M, Scorza G, Pietraforte D. Peroxynitrite induces long lived tyrosyl radicals in oxyhemoglobin of red blood cells through a reaction involving CO2 and a ferryl species. Biochemistry 1999; 38:2078–2087.

    PubMed  CAS  Google Scholar 

  52. van Jaarsveld H, Kuyl JM, Alberts DW. Exposure of rats to low concentrations of cigarette smoke increases myocardial sensitivity to ischaemia/reperfusion. Basic Res Cardiol 1992; 87:393–399.

    PubMed  Google Scholar 

  53. Alexander RW. Atherosclerosis as disease of redox-sensitive genes. Trans Am Clin Climatol Assoc 1998; 109:129–145.

    PubMed  CAS  Google Scholar 

  54. Alexander RW. Hypertension and the pathogenesis of atherosclerosis: oxidative stress and the mediation of arterial inflammatory response: a new perspective. Hypertension 1995; 25:155–161.

    PubMed  CAS  Google Scholar 

  55. Berliner JA, Navab M, Fogelman AM, Frank JS, Demer LL, Edwards PA et al. Atherosclerosis: basic mechanisms. Oxidation, inflammation, and genetics. Circulation 1995; 91:2488–2496.

    PubMed  CAS  Google Scholar 

  56. Parthasarathy S, Rankin SM. Role of oxidized low density lipoprotein in atherogenesis. Prog Lipid Res 1992; 31:127–143.

    PubMed  CAS  Google Scholar 

  57. Taylor AE, Johnson DC, Kazemi H. Environmental tobacco smoke and cardiovascular disease. Circulation 1992; 86:1–4.

    Google Scholar 

  58. Glantz S, Parmley W. Passive smoking and heart disease; epidemiology, physiology, and biochemistry. Circulation 1991; 83:1–12.

    PubMed  CAS  Google Scholar 

  59. Glantz S, Parmley W. Passive smoking and heart disease. J Am Med Assoc 1995; 273:1047–1053.

    CAS  Google Scholar 

  60. Steenland K. Passive smoking and the risk of heart disease. J Am Med Assoc 1992; 267:94–99.

    CAS  Google Scholar 

  61. Steenland K, Thun M, Lally C, Heath C. Environmental tobacco smoke and coronary heart disease in the American Cancer Society CPS-II Cohort. Circulation 1996; 94:622–628.

    PubMed  CAS  Google Scholar 

  62. Reilly M, Delanty N, Lawson JA, Fitzgerald GA. Modulation of oxidant stress in vivo in chronic cigarette smokers. Circulation 1996; 94:19–25.

    PubMed  CAS  Google Scholar 

  63. Reilly M, Pratico D, Delanty N et al. Increased formation of distinct F2 isoprostanes in hyper-cholesterolemia. Circulation 1998; 98:2822–2828.

    PubMed  CAS  Google Scholar 

  64. Pratico D, Tangirala RK, Rader DJ, Rokach J, FitzGerald GA. Vitamin E suppresses isopros-tane generation in vivo and reduces atherosclerosis in apoE deficient mice. Nat Med 1998; 4(10):1189–1192.

    PubMed  CAS  Google Scholar 

  65. Pratico D, Barry OP, Lawson JA, Adiyaman M, Hwang S-W, Khanapure SP et al. IPF2a-I: an index of lipid peroxidation in humans. Proc Natl Acad Sci U S A 1998; 95:3449–3454.

    PubMed  CAS  Google Scholar 

  66. Ito H, Torii M, Suzuki T. Decreased superoxide dismutase activity and increased superoxide anion production in cardiac hypertrophy of spontaneously hypertensive rats. Clin Exp Hypertens 1995; 17:803–816.

    PubMed  CAS  Google Scholar 

  67. Watts GF, Playford DA. Dyslipoproteinaemia and hyperoxidative stress in the pathogenesis of endothelial dysfunction in a non-insulin dependent diabetes mellitus: an hypothesis. Atherosclerosis 1998; 141:17–30.

    PubMed  CAS  Google Scholar 

  68. Rousselot DB, Bastard JP, Jaudon MC. Consequences of the diabetic status on the oxidant/ antioxidant balance. Diabetes Metab 2000; 26:163–176.

    Google Scholar 

  69. Wallace D. Mitochondrial diseases in man and mouse. Science 1999; 283:1482–1488.

    PubMed  CAS  Google Scholar 

  70. Wallace DC. A mitochondrial paradigm for degenerative diseases and ageing. Novartis Found Symp 2001; 235:247–263.

    PubMed  CAS  Google Scholar 

  71. Wallace DC. The mitochondrial genome in human adaptive radiation and disease: On the road to therapeutics and performance enhancement. Gene 2005; 354:169–180.

    PubMed  CAS  Google Scholar 

  72. Wallace DC. A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu Rev Genet 2005; 39:359–407.

    PubMed  CAS  Google Scholar 

  73. Ballinger SW. Mitochondrial dysfunction in cardiovascular disease. Free Radic Biol Med 2005; 38(10):1278–1295.

    PubMed  CAS  Google Scholar 

  74. Ballinger SW, Shoffner JM, Wallace DC. Mitochondrial myopathies-genetic-aspects. Curr Top Bioenerg 1994;17:59–98.

    CAS  Google Scholar 

  75. Wallace DC, Shoffner JM, Trounce I et al. Mitochondrial-DNA mutations in human degenerative diseases and aging. Biochim Biophys Acta 1995; 1271(1):141–151.

    PubMed  Google Scholar 

  76. Quintero M, Colombo SL, Godfrey A, Moncada S. Mitochondria as signaling organelles in the vascular endothelium. Proc Natl Acad Sci U S A 2006; 103(14):5379–5384.

    PubMed  CAS  Google Scholar 

  77. Zhang Y, Marcillat O, Giulivi C, Ernster L, Davies KJ. The oxidative inactivation of mitochondrial electron transport chain components and ATPase. J Biol Chem 1990; 265:16330–16336.

    PubMed  CAS  Google Scholar 

  78. Turrens JF. Mitochondrial formation of reactive oxygen species. J Physiol 2003; 552(2):335–344.

    PubMed  CAS  Google Scholar 

  79. Lambert A, Brand M. Superoxide production by NADH:ubiquinone oxidoreductase (complex I) depends on the pH gradient across the mitochondrial inner membrane. Biochem J 2004.

    Google Scholar 

  80. Liu Y, Fiskum G, Schubert D. Generation of reactive oxygen species by the mitochondrial electron transport chain. J Neurochem 2002; 80:780–787.

    PubMed  CAS  Google Scholar 

  81. Han D, Canali R, Rettori D, Kaplowitz N. Effect of glutathione depletion on sites and topology of superoxide and hydrogen peroxide production in mitochondria. Mol Pharmacol 2003; 64(5):1136–1144.

    PubMed  CAS  Google Scholar 

  82. Forman HJ, Boveris A. In: Prior WA, ed. Free radicals in biology. Orlando, Florida: Academic Press, 1982: 65–90.

    Google Scholar 

  83. Forman HJ, Boveris A. Superoxide radical and hydrogen peroxide in mitochondria. In: Prior WA, ed. Free radicals in biology. Orlando, Florida: Academic Press, 1982: 65–90.

    Google Scholar 

  84. Boveris A, Turrens JF. Production of superoxide anion by the NADH dehydrogenase of mammalian mitochondria. In: Bannister J, Hill H, eds. Chemical and biochemical aspects of superoxide and superoxide dismutase. Amsterdam: Elsevier, 1980: 84–91.

    Google Scholar 

  85. Turrens JF, Boveris A. Generation of superoxide anion by the NADH dehydrogenase of bovine heart mitochondria. Biochem J 1980; 191:421–427.

    PubMed  CAS  Google Scholar 

  86. Chance B, Sies H, Boveris A. Hydroperoxide metabolism in mammalian organs. Physiol Rev 1979; 59:527–605.

    PubMed  CAS  Google Scholar 

  87. Ide T, Tsutsui H, Kinugawa S et al. Direct evidence for increased hydroxyl radicals orginat-ing from superoxide in the failing myocardium. Circ Res 2000; 86:152–157.

    PubMed  CAS  Google Scholar 

  88. Baas AS, Berk BC. Differential activation of mitogen-activated protein kinases by H2O2 and O2 •− in vascular smooth muscle cells. Circ Res 1995; 77(1):29–36.

    PubMed  CAS  Google Scholar 

  89. Chen K, Vita JA, Berk BC, Keaney JF Jr. c-Jun-N-terminal kinase activation by hydrogen peroxide in endothelial cells involves Src-dependent epidermal growth factor receptor trans-activation. J Biol Chem 2001; 276(19):16045–16050.

    PubMed  CAS  Google Scholar 

  90. Guyton KZ, Liu Y, Gorospe M, Xu Q, Holbrook NJ. Activation of mitogen-activated protein kinase by H2O2. J Biol Chem 1996; 271:4138–4142.

    PubMed  CAS  Google Scholar 

  91. Kim SM, Byun JS, Jung YD et al. The effects of oxygen radicals on the activity of nitric oxide synthase and guanylate cyclase. E. Exp Mol Med 1998; 30(4):221–6.

    CAS  Google Scholar 

  92. Sundaresan M, Yu ZX, Fererans VJ, Irani K, Finkel T. Requirement for generation of H202 for platelet-derived growth factor signal transduction. Science 1995; 270:296–299.

    PubMed  CAS  Google Scholar 

  93. Schulze-Osthoff K, Los M, Baeuerle PA. Redox signaling by transcription factors NF-kB and AP-1 in lymphocytes. Biochem Pharmacol 1995; 50:735–741.

    PubMed  CAS  Google Scholar 

  94. Devary Y, Rosette C, DiDonato JA, Karin M. NF-κB activation by ultraviolet light not dependent on a nuclear signal. Science 1993; 261:1442–1445.

    PubMed  CAS  Google Scholar 

  95. Mohan N, Meltz MM. Induction of nuclear factor κB after low-dose ionizing radiation involves a reactive oxygen intermediate signaling pathway. Radic Res 1994; 140:97–104.

    CAS  Google Scholar 

  96. Schulze-Osthoff K, Beyaert R, Vandervoorde V, Haegeman G, Fiers W. Depletion of the mitochondrial electron transport abrogates the cytotoxic and gene-inductive effects of TNF EMBO J 1993; 12:3095–3104.

    CAS  Google Scholar 

  97. Chen K, Thomas SR, Albano A, Murphy MP, Keaney JF. Mitochondrial function is required for hydrogen peroxide-induced growth factor receptor transactivation and downstream signaling. J Biol Chem 2004; 279:35079–35086.

    PubMed  CAS  Google Scholar 

  98. Manna SK. Overexpression of manganese superoxide dismutase suppresses tumor necrosis factor-induced apoptosis and activation of nuclear transcription factor-kappaB and activated protein-1. J Biol Chem 1998; 273:13245–13254.

    PubMed  CAS  Google Scholar 

  99. Schulze-Osthoff K, Bakker AC, Vanhaesebroeck B, Beyaert R, Jacob WA , Fiers W. Cytotoxic activity of tumor necrosis factor is mediated by early damage of mitochondrial functions. Evidence for the involvement of mitochondrial radical generation. J Biol Chem 1992; 267(8):5317–5323.

    PubMed  CAS  Google Scholar 

  100. Maehara K, Oh-Hashi K, Isobe K-I. Early growth-responsive-1-dependent manganese super-oxide dismutase gene transcription mediated by platelet-derived growth factor. FASEB J 2001; 15(11):2025–2026.

    PubMed  CAS  Google Scholar 

  101. Clementi E, Brown G, Foxwell N, Moncada S. On the mechanism by which vascular endothelial cells regulate their oxygen consumption. Proc Natl Acad Sci U S A 1999; 96:1559–1562.

    PubMed  CAS  Google Scholar 

  102. Moncada S, Erusalimsky JD. Does nitric oxide modulate mitochondrial energy generation and apoptosis? Nat Rev Mol Cell Biol 2002; 3(3):214–220.

    PubMed  CAS  Google Scholar 

  103. Cassina A, Radi R. Differential inhibitory action of nitric oxide and peroxynitrite on mito-chondrial electron transport. Arch Biochem Biophys 1996; 328:309–316.

    PubMed  CAS  Google Scholar 

  104. Ramachandran A, Levonen AL, Brookes PS et al. Mitochondria, nitric oxide, and cardiovascular dysfunction. Free Radic Biol Med 2002; 33(11):1465–1474.

    PubMed  CAS  Google Scholar 

  105. Ramachandran A, Moellering DR, Ceaser E, Shiva S, Xu J, Darley-Usmar VM. Inhibition of mitochondrial protein synthesis results in increased endothelial cell susceptibility to nitric oxide-induced apoptosis. Proc Natl Acad Sci U S A 2002; 99(10):6643–6648.

    PubMed  CAS  Google Scholar 

  106. Kissner R, Nauser T, Bugnon P, Lye PG, Loppenol WH. Formation and properties of perox-ynitrite as studied by laser flash photolysis, high-pressure stopped-flow technique, and pulse radiolysis. Chem Res Toxicol 1997; 10:1285–1292.

    PubMed  CAS  Google Scholar 

  107. Ramachandran A, Ceaser E, Darley-Usmar VM. Chronic exposure to nitric oxide alters the free iron pool in endothelial cells: role of mitochondrial respiratory complexes and heat shock proteins. Proc Natl Acad Sci U S A 2004; 101:384–389.

    PubMed  CAS  Google Scholar 

  108. Beckman JS. Oxidative damage and tyrosine nitration from peroxynitrite. Chem Res Toxicol 1996; 9:836–844.

    PubMed  CAS  Google Scholar 

  109. Garlid KD, Jaburek M, Jezek P. Mechanism of uncoupling proteins action. Biochem Soc Trans 2001; 29:803–806.

    PubMed  CAS  Google Scholar 

  110. Jaburek M, Varecha M, Gimeno RE et al. Transport function and regulation of mitochondrial uncoupling proteins 2 and 3. J Biol Chem 1999; 274:26003–26007.

    PubMed  CAS  Google Scholar 

  111. Klingenberg M, Winkler E, Echtay K. Uncoupling protein, H+ transport and regulation. Biochem Soc Trans 2001; 29:806–811.

    PubMed  CAS  Google Scholar 

  112. Nedergaard J, Golozoubova V, Matthias A, Shabalina I, Ohba K, Ohlson K et al. Life without UCP1: mitochondrial, cellular, and organismal characteristics of the UCP1-ablated mice. Biochem Soc Trans 2001; 29:756–763.

    PubMed  CAS  Google Scholar 

  113. Stuart JA, Cadenas S, Jacobsons MB, Roussel D, Brand MD. Mitochondrial proton leak and the uncoupling protein 1 homologues. Biochim Biophys Acta 2001; 1504:144–158.

    PubMed  CAS  Google Scholar 

  114. Dulloo AG, Samec S, Seydoux J. Uncoupling protein 3 and fatty acid metabolism. Biochem Soc Trans 2001; 29:785–791.

    PubMed  CAS  Google Scholar 

  115. Nedergaard J, Cannon B. The “novel” “uncoupling” proteins UCP2 and UCP3: what do they really do? Pros and cons for suggested functions. Exp Physiol 2003; 88:65–84.

    PubMed  CAS  Google Scholar 

  116. Talbot DA, Lambert AJ, Brand MD. Production of endogenous matrix superoxide from mitochondrial complex I leads to activation of uncoupling protein 3. FEBS Lett 2004; 556:111–115.

    PubMed  CAS  Google Scholar 

  117. Yan L-J, Sohal RS. Mitochondrial adenine nucleotide translocase is modified oxidatively during aging. Proc Natl Acad Sci U S A 1998; 95:12896–12901.

    PubMed  CAS  Google Scholar 

  118. Yakes FM, Van Houten B. Mitochondrial DNA damage is more extensive and persists longer than nuclear DNA damage in human cells following oxidative stress. Proc Natl Acad Sci USA 1997; 94:514–519.

    PubMed  CAS  Google Scholar 

  119. MacMillan-Crow LA, Crow JP, Thompson JA. Peroxynitrite-mediated inactivation of manganese superoxide dismutase involves nitration and oxidation of critical gyrosine residues. Biochemistry 1998; 37:1613–1622.

    PubMed  CAS  Google Scholar 

  120. Duan J, Karmazyn M. Relationship between oxidative phosphorylation and adenine nucle-otide translocase activity in two populations of cardiac mitochondria and mechanical recovery of ischemic hearts following reperfusion. Can J Physiol Pharmacol 1989; 67:704–709.

    PubMed  CAS  Google Scholar 

  121. Ballinger SW, Patterson WC, Yan C-N, Doan R, Burow DL, Young CG et al. Hydrogen peroxide and peroxynitrite induced mitochondrial DNA damage and dysfunction in vascular endothelial and smooth muscle cells. Circ Res 2000; 86:960–966.

    PubMed  CAS  Google Scholar 

  122. Ballinger SW, Patterson C, Knight-Lozano CA, Burow DL, Conklin CA, Hu Z et al. Mitochondrial integrity and function in atherogenesis. Circulation 106, 544–549. 2002.

    Google Scholar 

  123. Knight-Lozano CA, Young CG, Burow DL et al. Cigarette smoke exposure and hypercholes-terolemia increase mitochondrial damage in cardiovascular tissues. Circulation 105, 849–854. 2002.

    Google Scholar 

  124. Corral-Debrinski M, Stepien G, Shoffner JM, Lott MT, Kanter K, Wallace DC. Hypoxemia is associated with mitochondrial DNA damage and gene induction: implications for cardiac disease. J Am Med Assoc 1991; 266:1812–1816.

    CAS  Google Scholar 

  125. Corral-Debrinski M, Shoffner JM, Lott MT, Wallace DC. Association of mitochondrial DNA damage with aging and coronary atherosclerotic heart disease. Mutat Res 1992; 275:169–180.

    PubMed  CAS  Google Scholar 

  126. Aliev G, Seyidova D, Neal ML et al. Atherosclerotic lesions and mitochondria DNA deletions in brain microvessels as a central target for the development of human AD and AD-like pathology in aged transgenic mice. Ann NY Acad Sci 2002; 977:45–64.

    PubMed  CAS  Google Scholar 

  127. Brookes PS, Zhang J, Dai L et al. Increased sensitivity of mitochondrial respiration to inhibition by nitric oxide in cardiac hypertrophy. J Mol Cell Cardiol 2001; 33(1):69–82.

    PubMed  CAS  Google Scholar 

  128. Blanc J, Alves-Guerra MC, Esposito B, Rousset S, Gourdy P, Ricquier D et al. Protective role of uncoupling protein 2 in atherosclerosis. Circulation 2003; 107:388–390.

    PubMed  CAS  Google Scholar 

  129. Asimakis G, Lick S, Patterson W. Postischemic recovery of contractile function is impaired in SOD2+/− but not SOD1+/− mouse hearts. Circulation 2002; 105(8):981–986.

    PubMed  CAS  Google Scholar 

  130. Chen Z, Siu B, Ho Y-S, Vincent R, Chua CC, Hamdy RC et al. Overexpression of MnSOD protects against myocardial ischemia/reperfusion injury in transgenic mice. J Mol Cell Cardiol 1998; 30:2281–2289.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  132. Bienengraeber M, Ozcan C, Terzic A. Stable transfection of UCP1 confers resistance to hypoxia/reoxygenation in a heart-derived cell line. J Mol Cell Cardiol 2003; 35:861–865.

    PubMed  CAS  Google Scholar 

  133. Ide T, Tsutsui H, Hayashidani S et al. Mitochondrial DNA damage and dysfunction associated with oxidative stress in failing hearts after myocardial infarction. Circ Res 2001; 88:529–535.

    PubMed  CAS  Google Scholar 

  134. Bernal-Mizrachi C, Gates AC, Weng S et al. Vascular respiratory uncoupling increases blood pressure and atherosclerosis. Nature 2005; 435(7041):502–506.

    PubMed  CAS  Google Scholar 

  135. Bernal-Mizrachi C, Weng S, Li B et al. Respiratory uncoupling lowers blood pressure through a leptin-dependent mechanism in genetically obese mice. Arterioscler Thromb Vasc Biol 2002; 22(6):961–968.

    PubMed  CAS  Google Scholar 

  136. Yang H, Roberts LJ, Shi MJ et al. Retardation of atherosclerosis by overexpression of cata-lase or both Cu/Zn-superoxide dismutase and catalase in mice lacking apolipoprotein E. Circ Res 2004; 95(11):1075–1081.

    PubMed  CAS  Google Scholar 

  137. Ceaser E, Ramachandran A, Levonen AL, Darley-Usmar VM. Oxidized low-density lipopro-tein and 15-deoxy-delta12,14-PGJ2 increase mitochondrial complex I activity in endothelial cells. Am J Physiol 2003; 285:H2298–H2308.

    CAS  Google Scholar 

  138. Kinscherf R, Deigner H-P, Usinger C et al. Induction of mitochondrial manganese superox-ide dismutase in macrophages by oxidized LDL: its relevance in atherosclerosis of humans and heritable hyperlipidemic rabbits. FASEB J 1997; 11:1317–1328.

    PubMed  CAS  Google Scholar 

  139. Asmis R, Begley JG. Oxidized LDL promotes peroxide mediated mitochondrial dysfunction and cell death in human macrophages. Circ Res 2003; 92:e20–e29.

    PubMed  CAS  Google Scholar 

  140. Mabile L, Meilhac O, Escargueil-Blanc I, Troly M, Pieraggi M-T, Salvayre R et al. Mitochondrial function is involved in LDL oxidation mediated by human cultured endothe-lial cells. Arterioscler Thromb Vasc Biol 1997; 17:1575–1582.

    PubMed  CAS  Google Scholar 

  141. Mikaelian NP, Khalilov EM, Ivanov AS, Fortinskaia ES, Lopukhin IM. Mitochondrial enzymes in circulating lymphocytes during hemosorption for experimental hypercholestero-lemia. Biull Eksp Biol Med 1983; 96(9):35–37.

    PubMed  CAS  Google Scholar 

  142. Nishikawa T, Edelstein D, Du XL, Yamagishi S, Matsumura T, Kaneda Y et al. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 2000; 404(6779):787–790.

    PubMed  CAS  Google Scholar 

  143. Nishikawa T, Edelstein D, Brownlee M. The missing link: a single unifying mechanism for diabetic complications. Kidney Int 2000; 58:26–30.

    Google Scholar 

  144. Vega-Lopez S, Devaraj S, Jialal I. Oxidative stress and antioxidant supplementation in the management of diabetic cardiovascular disease. J Invest Med 2004; 52(1):24–32.

    CAS  Google Scholar 

  145. Venugopal SK, Devaraj S, Yang T, Jialal I. alpha-Tocopherol decreases superoxide anion release in human monocytes under hyperglycemic conditions via inhibition of protein kinase C-alpha. Diabetes 2002; 51(10):3049–3054.

    PubMed  CAS  Google Scholar 

  146. Venugopal SK, Devaraj S, Yang TTC. Alpha tocopherol decreases superoxide anion release in THP-1 cells under hyperglycemic conditions through inhibition of PKC-a. Diabetes 2002; 51:3049–3054.

    PubMed  CAS  Google Scholar 

  147. Azevedo-Martins AK, Lortz S, Lenzen S, Curi R, Eizirik DL, Tiedge M. Improvement of the mitochondrial antioxidant defense status prevents cytokine-induced nuclear factor-kB activation in insulin-producing cells. Diabetes 2003; 52:93–101.

    PubMed  CAS  Google Scholar 

  148. Nyholm B, Fisker S, Lund S, Moller N, Schmitz O. Increased circulating leptin concentrations in insulin-resistant first-degree relatives of patients with non-insulin-dependent diabetes mellitus: relationship to body composition and insulin sensitivity but not to family history of non-insulin-dependent diabetes mellitus. Eur J Endocrinol 1997; 136(2):173–179.

    PubMed  CAS  Google Scholar 

  149. Rudberg S, Persson B. Serum leptin levels in young females with insulin-dependent diabetes and the relationship to hyperandrogenicity and microalbuminuria. Horm Res 1998; 50(6):297–+.

    PubMed  CAS  Google Scholar 

  150. Maffei M, Halaas J, Ravussin E et al. Leptin levels in human and rodent: measurement of plasma leptin and Ob RNA in obese and weight-reduced subjects. Nat Med 1995; 1(11):1155–1161.

    PubMed  CAS  Google Scholar 

  151. Yamagishi S, Edelstein D, Du XL, Kaneda Y, Guzman M, Brownlee M. Leptin induces mitochondrial superoxide production and monocyte chemoattractant protein-1 expression in aortic endothelial cells by increasing fatty acid oxidation via protein kinase A. J Biol Chem 2001; 276(27):25096–25100.

    PubMed  CAS  Google Scholar 

  152. Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D et al. Weight-reducing effects of the plasma-protein encoded by the Obese gene. Science 1995; 269(5223):543–546.

    PubMed  CAS  Google Scholar 

  153. Pelleymounter MA, Cullen MJ, Baker MB et al. Effects of the Obese gene-product on body-weight regulation in Ob/Ob mice. Science 1995; 269(5223):540–543.

    PubMed  CAS  Google Scholar 

  154. Sierra-Honigmann MR, Nath AK, Murakami C, Garcia-Cardena G, Papapetropoulos A, Sessa WC et al. Biological action of leptin as an angiogenic factor. Science 1998; 281(5383):1683–1686.

    PubMed  CAS  Google Scholar 

  155. Bouloumie A, Marumo T, Lafontan M, Busse R. Leptin induces oxidative stress in human endothelial cells. FASEB J 1999; 13(10):1231–1238.

    PubMed  CAS  Google Scholar 

  156. Pueyo ME, Gonzales W, Nicoletti A, Savoie F, Arnal J-F, Michel J-B. Angiotensin II stimulates endothelial vascular cell adhesion molecule-1 via nuclear transcription factor-kB activation induced by intracellular oxidative stress. Arterioscler Thromb Vasc Biol 2000; 20:645–651.

    PubMed  CAS  Google Scholar 

  157. American Heart Association. Heart disease and stroke statistics-2005 Update. 1a-60. 2005. Dallas, TX, American Heart Association.

    Google Scholar 

  158. Gvozdjak J, Gvozdjakova A, Kucharska J, Bada V. The effect of smoking on myocardial metabolism. Czech Med 1987; 10:47–53.

    PubMed  CAS  Google Scholar 

  159. Gvozdjakova A, Kucharska J, Gvozdjak J. Effect of smoking on the oxidative processes of cardiomyocytes. Cardiology 1992; 1992:81–84.

    Google Scholar 

  160. van Jaarsveld H, Kuyl JM, Alberts DW. Antioxidant vitamin supplementation of smoke exposed rats partially protects against myocardial ischemic/reperfusion injury. Free Radic Res Commun 1992; 17:263–269.

    PubMed  Google Scholar 

  161. Davis J, Shelton L, Watnabe I, Arnold J. Passive smoking affects endothelium and platelets. Arch Intern Med 1989; 149:386–389.

    PubMed  CAS  Google Scholar 

  162. Lu KP, Alejandro NF, Taylor KM, Joyce MM, Spencer TE, Ramos KS. Differential expression of ribosomal L31, Zis, gas-5 and mitochondrial mRNAs following oxidant induction of proliferative vascular smooth muscle cell phenotypes. Atherosclerosis 2002; 160:273–280.

    PubMed  CAS  Google Scholar 

  163. Willett WC. Balancing life-style and genomics research for disease prevention. Science 2002; 296(5568):695–698.

    PubMed  CAS  Google Scholar 

  164. Connelly JJ, Wang T, Cox JE et al. GATA2 is associated with familial early-onset coronary artery disease. PloS Genet 2006; 2(8):1265–1273.

    CAS  Google Scholar 

  165. Humphries SE, Talmud PJ, Hawe E, Bolla M, Day INM, Miller GJ. Apolipoprotein E4 and coronary heart disease in middle-aged men who smoke: a prospective study. Lancet 2001; 358(9276):115–119.

    PubMed  CAS  Google Scholar 

  166. Talmud PJ, Humphries SE. Gene: environment interaction in lipid metabolism and effect on coronary heart disease risk. Curr Opin Lipidol 2002; 13(2):149–154.

    PubMed  CAS  Google Scholar 

  167. Keavney B, Parish S, Palmer A et al. Large-scale evidence that the cardiotoxicity of smoking is not significantly modified by the apolipoprotein E epsilon 2/epsilon 3/epsilon 4 genotype. Lancet 2003; 361(9355):396–398.

    PubMed  CAS  Google Scholar 

  168. Wheeler JG, Keavney BD, Watkins H, Collins R, Danesh J. Four paraoxonase gene polymorphisms in 11,212 cases of coronary heart disease and 12,786 controls: meta-analysis of 43 studies. Lancet 2004; 363(9410):689–695.

    PubMed  CAS  Google Scholar 

  169. Ishida BY, Blanche PJ, Nichols AV, Yashar M, Paigen B. Effects of atherogenic diet consumption on lipoproteins in mouse strains C57Bl/6 and C3H. J Lipid Res 1991; 32(4):559–568.

    PubMed  CAS  Google Scholar 

  170. Wang XS, Ria M, Kelmenson PM et al. Positional identification of TNFSF4, encoding OX40 ligand, as a gene that influences atherosclerosis susceptibility. Nat Genet 2005; 37(4):365–372.

    PubMed  CAS  Google Scholar 

  171. van Schooten FJ, Hirvonen A, Maas LM et al. Putative susceptibility markers of coronary artery disease: association between VDR genotype, smoking, and aromatic DNA adduct levels in human right atrial tissue. FASEB J 1998; 12(13):1409–1417.

    PubMed  Google Scholar 

  172. Stephens JW, Humphries SE. The molecular genetics of cardiovascular disease: clinical implications. J Int Med 2003; 253(2):120–127.

    CAS  Google Scholar 

  173. Tabibiazar R, Wagner RA, Spin JM, Ashley EA, Narasimhan B, Rubin EM et al. Mouse strain-specific differences in vascular wall gene expression and their relationship to vascular disease. Arterioscler Thromb Vasc Biol 2005; 25(2):302–308.

    PubMed  CAS  Google Scholar 

  174. Tabibiazar R, Wagner RA, Ashley EA et al. Signature patterns of gene expression in mouse atherosclerosis and their correlation to human coronary disease. Physiol Genomics 2005; 22(2):213–226.

    PubMed  CAS  Google Scholar 

  175. Ruiz-Pesini E, Mishmar D, Brandon M, Procaccio V, Wallace DC. Effects of purifying and adaptive selection on regional variation in human mtDNA. Science 2004; 303:223–226.

    PubMed  CAS  Google Scholar 

  176. Ballinger SW, Shoffner JM, Hedaya EV et al. Maternally transmitted diabetes and deafness associated with a 10.4 kb mitochondrial DNA deletion. Nat Genet 1992; 1:11–15.

    PubMed  CAS  Google Scholar 

  177. Corral-Debrinski M, Horton T, Lott MT, Shoffner JM, Beal MF, Wallace DC. Mitochondrial DNA deletions in human brain: regional variability and increase with advanced age. Nat Genet 1992; 2(4):324–329.

    PubMed  CAS  Google Scholar 

  178. Shoffner JM, Lott MT, Lezza AM, Seibel P, Ballinger SW, Wallace DC. Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNA tRNA(Lys) mutation. Cell 1990; 61(6):931–937.

    PubMed  CAS  Google Scholar 

  179. Wallace DC, Singh G, Lott MT et al. Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy. Science 1988; 242(4884):1427–1430.

    PubMed  CAS  Google Scholar 

  180. Wallace DC, Zheng XX, Lott MT et al. Familial mitochondrial encephalomyopathy (MERRF): genetic, pathophysiological, and biochemical characterization of a mitochondrial DNA disease. Cell 1988; 55(4):601–610.

    PubMed  CAS  Google Scholar 

  181. Brown MD, Sun FZ, Wallace DC. Clustering of Caucasian Leber hereditary optic neuropathy patients containing the 11778 or 14484 mutations on an mtDNA lineage. Am J Hum Genet 1997; 60(2):381–387.

    PubMed  CAS  Google Scholar 

  182. Brown MD, Starikovskaya E, Derbeneva O et al. The role of mtDNA background in disease expression: a new primary LHON mutation associated with Western Eurasian haplogroup J. Hum Genet 2002; 110(2):130–138.

    CAS  Google Scholar 

  183. Brown MD, Zhadanov S, Allen JC et al. Novel mtDNA mutations and oxidative phosphor-ylation dysfunction in Russian LHON families. Hum Genet 2001; 109(1):33–39.

    PubMed  CAS  Google Scholar 

  184. Brown MD, Derbeneva OA, Starikovskaya Y, Allen J, Sukernik RI, Wallace DC. The influence of mtDNA background on the disease process: a new primary Leber's Hereditary Optic Neuropathy mtDNA mutation requires European haplogroup J for expression. American Journal of Human Genetics 2001; 69(4):578.

    Google Scholar 

  185. Petros JA, Baumann AK, Ruiz-Pesini E et al. mtDNA mutations increase tumorigenicity in prostate cancer. Proc Natl Acad Sci U S A 2005; 102(3):719–724.

    PubMed  CAS  Google Scholar 

  186. Chagnon P, Gee M, Filion M, Robitaille Y, Belouchi M, Gauvreau D. Phylogenetic analysis of the mitochondrial genome indicates significant differences between patients with Alzheimer disease and controls in a French-Canadian founder population. Am J Med Genet 1999; 85(1):20–30.

    PubMed  CAS  Google Scholar 

  187. De Benedictis G, Rose G, Carrieri G, De Luca M, Falcone E, Passarino G et al. Mitochondrial DNA inherited variants are associated with successful aging and longevity in humans. FASEB J 1999; 13(12):1532–1536.

    PubMed  Google Scholar 

  188. Rose G, Passarino G, Carrieri G et al. Paradoxes in longevity: sequence analysis of mtDNA haplogroup J in centenarians. Eur J Hum Genet 2001; 9(9):701–707.

    PubMed  CAS  Google Scholar 

  189. van der Walt JM, Nicodemus KK, Martin ER et al. Mitochondrial polymorphisms significantly reduce the risk of Parkinson disease. Am J Hum Genet 2003; 72(4):804–811.

    PubMed  Google Scholar 

  190. van der Walt JM, Dementieva YA, Martin ER et al. Analysis of European mitochondrial haplogroups with Alzheimer disease risk. Neurosci Lett 2004; 365(1):28–32.

    PubMed  Google Scholar 

  191. Johnson KR, Zheng QY, Bykhovskaya Y, Spirina O, Fischel-Ghodsian N. A nuclear-mitochondrial DNA interaction affecting hearing impairment in mice. Nat Genet 2001; 27(2):191–194.

    PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by National Institutes of Health grants ES11172, HL77419 and DK79626.

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  1. Division of Molecular and Cellular Pathology, University of Alabama at Birmingham, Birmingham, AL

    Scott W. Ballinger

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  1. Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK

    Satomi Miwa PhD

  2. Functional Genomics Core, Children's Hospital Oakland Research Institute, Oakland, CA, USA

    Kenneth B. Beckman PhD

  3. Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

    Florian L. Muller PhD

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Ballinger, S.W. (2008). Deregulation of Mitochondrial Function: A Potential Common Theme for Cardiovascular Disease Development. In: Miwa, S., Beckman, K.B., Muller, F.L. (eds) Oxidative Stress in Aging. Aging Medicine. Humana Press. https://doi.org/10.1007/978-1-59745-420-9_10

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