Skip to main content
SpringerLink
Log in

Oxidative Stress and Cardiovascular Fibrosis

  • Chapter
  • First Online:
Studies on Cardiovascular Disorders

  • 726 Accesses

Abstract

Oxidative stress is defined as an imbalance of the generation of reactive oxygen species (ROS) in excess of the capacity of cells/tissues to detoxify or scavenge them. Such a state of oxidative stress may alter the structure/function of cellular macromolecules that eventually leads to tissue/organ dysfunction. The harmful effects of ROS have been largely attributed to its indiscriminate, stochastic effects on the oxidation of protein, lipids, or DNA. Alternatively, detrimental effects of ROS may be mediated by aberrant “redox signaling” in specific pathophysiologic contexts. Cardiovascular disease is a major cause of morbidity and mortality in industrialized nations. Acute myocardial infarction from atherosclerotic coronary artery disease often results in remodeling responses of the myocardium that may culminate in congestive heart failure. Another important cause of CHF is chronic pressure overload due to systemic hypertension. We discuss mechanisms by which oxidative stress contributes to the pathogenesis of vascular disease, endothelial dysfunction, and cardiovascular fibrosis. Identifying specific pathways for ROS generation and roles in cardiovascular fibrosis could lead to rational design of drugs that promote tissue repair/regeneration, while attenuating the progression of CHF.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 299.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Thannickal VJ (2009) Oxygen in the evolution of complex life and the price we pay. Am J Respir Cell Mol Biol 40(5):507–510; Epub 2008 Oct 31

    Article  PubMed  CAS  Google Scholar 

  2. Lambeth JD (2007) Nox enzymes, ROS, and chronic disease: an example of antagonistic pleiotropy. Free Radic Biol Med 43:332–347

    Article  PubMed  CAS  Google Scholar 

  3. Murdoch CE, Zhang M, Cave AC et al (2006) NADPH oxidase-dependent redox signalling in cardiac hypertrophy, remodelling and failure. Cardiovasc Res 71:208–215

    Article  PubMed  CAS  Google Scholar 

  4. Sun Y (2007) Oxidative stress and cardiac repair/remodeling following infarction. Am J Med Sci 334:197–205

    Article  PubMed  Google Scholar 

  5. Rosamond W, Flegal K, Furie K et al (2008) Heart disease and stroke statistics–2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 117:e25–e146

    Article  PubMed  Google Scholar 

  6. Wild S, Roglic G, Green A et al (2004) Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27:1047–1053

    Article  PubMed  Google Scholar 

  7. Schocken DD, Benjamin EJ, Fonarow GC et al (2008) Prevention of heart failure: a scientific statement from the American Heart Association Councils on Epidemiology and Prevention, Clinical Cardiology, Cardiovascular Nursing, and High Blood Pressure Research; Quality of Care and Outcomes Research Interdisciplinary Working Group; and Functional Genomics and Translational Biology Interdisciplinary Working Group. Circulation 117:2544–2565

    Article  PubMed  Google Scholar 

  8. Bonetti PO, Lerman LO, Lerman A (2003) Endothelial dysfunction: a marker of atherosclerotic risk. Arterioscler Thromb Vasc Biol 23:168–175

    Article  PubMed  CAS  Google Scholar 

  9. Ross R (1999) Atherosclerosis – an inflammatory disease. N Engl J Med 340:115–126

    Article  PubMed  CAS  Google Scholar 

  10. Deanfield JE, Halcox JP, Rabelink TJ (2007) Endothelial function and dysfunction: testing and clinical relevance. Circulation 115:1285–1295

    PubMed  Google Scholar 

  11. Qian Y, Feldman E, Pennathur S et al (2008) From fibrosis to sclerosis: mechanisms of glomerulosclerosis in diabetic nephropathy. Diabetes 57:1439–1445

    Article  PubMed  CAS  Google Scholar 

  12. Thannickal VJ, Toews GB, White ES et al (2004) Mechanisms of pulmonary fibrosis. Annu Rev Med 55:395–417

    Article  PubMed  CAS  Google Scholar 

  13. Aneja A, Tang WH, Bansilal S et al (2008) Diabetic cardiomyopathy: insights into pathogenesis, diagnostic challenges, and therapeutic options. Am J Med 121:748–757

    Article  PubMed  Google Scholar 

  14. Cai H (2005) NAD(P)H oxidase-dependent self-propagation of hydrogen peroxide and vascular disease. Circ Res 96:818–822

    Article  PubMed  CAS  Google Scholar 

  15. Guzik TJ, Harrison DG, Vascular NADPH (2006) Oxidases as drug targets for novel antioxidant strategies. Drug Discov Today 11:524–533

    Article  PubMed  CAS  Google Scholar 

  16. Ames BN, Shigenaga MK, Hagen TM (1993) Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci U S A 90:7915–7922

    Article  PubMed  CAS  Google Scholar 

  17. Baynes JW, Thorpe SR (2000) Glycoxidation and lipoxidation in atherogenesis. Free Radic Biol Med 28:1708–1716

    Article  PubMed  CAS  Google Scholar 

  18. Heinecke JW (2003) Oxidative stress: new approaches to diagnosis and prognosis in atherosclerosis. Am J Cardiol 91:12A–16A

    Article  PubMed  CAS  Google Scholar 

  19. Pennathur S, Heinecke JW (2007) Oxidative stress and endothelial dysfunction in vascular disease. Curr Diab Rep 7:257–264

    Article  PubMed  CAS  Google Scholar 

  20. Lin MT, Beal MF (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443:787–795

    Article  PubMed  CAS  Google Scholar 

  21. Butterfield DA (2006) Oxidative stress in neurodegenerative disorders. Antioxid Redox Signal 8:1971–1973

    Article  PubMed  CAS  Google Scholar 

  22. Brownlee M (1995) Advanced protein glycosylation in diabetes and aging. Annu Rev Med 46:223–234

    Article  PubMed  CAS  Google Scholar 

  23. Jay D, Hitomi H, Griendling KK (2006) Oxidative stress and diabetic cardiovascular complications. Free Radic Biol Med 40:183–192

    Article  PubMed  CAS  Google Scholar 

  24. Pennathur S, Heinecke JW (2007) Mechanisms for oxidative stress in diabetic cardiovascular disease. Antioxid Redox Signal 9:955–969

    Article  PubMed  CAS  Google Scholar 

  25. Cottone S, Lorito MC, Riccobene R et al (2008) Oxidative stress, inflammation and cardiovascular disease in chronic renal failure. J Nephrol 21:175–179

    PubMed  Google Scholar 

  26. Percy C, Pat B, Poronnik P et al (2005) Role of oxidative stress in age-associated chronic kidney pathologies. Adv Chronic Kidney Dis 12:78–83

    Article  PubMed  Google Scholar 

  27. Brownlee M (2001) Biochemistry and molecular cell biology of diabetic complications. Nature 414:813–820

    Article  PubMed  CAS  Google Scholar 

  28. Houstis N, Rosen ED, Lander ES (2006) Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature 440:944–948

    Article  PubMed  CAS  Google Scholar 

  29. Baynes JW, Thorpe SR (1999) Role of oxidative stress in diabetic complications: a new perspective on an old paradigm. Diabetes 48:1–9

    Article  PubMed  CAS  Google Scholar 

  30. Brown MS, Goldstein JL (1992) Koch’s postulates for cholesterol. Cell 71:187–188

    Article  PubMed  CAS  Google Scholar 

  31. Goldstein JL, Ho YK, Basu SK et al (1979) Binding site on macrophages that mediates uptake and degradation of acetylated low density lipoprotein, producing massive cholesterol deposition. Proc Natl Acad Sci U S A 76:333–337

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  33. Steinberg D (2002) Atherogenesis in perspective: hypercholesterolemia and inflammation as partners in crime. Nat Med 8:1211–1217

    Article  PubMed  CAS  Google Scholar 

  34. Haberland ME, Fong D, Cheng L (1988) Malondialdehyde-altered protein occurs in atheroma of Watanabe heritable hyperlipidemic rabbits. Science 241:215–218

    Article  PubMed  CAS  Google Scholar 

  35. Yla-Herttuala S, Palinski W, Butler SW et al (1994) Rabbit and human atherosclerotic lesions contain IgG that recognizes epitopes of oxidized LDL. Arterioscler Thromb 14:32–40

    Article  PubMed  CAS  Google Scholar 

  36. Yla-Herttuala S, Palinski W, Rosenfeld ME et al (1989) Evidence for the presence of oxidatively modified low density lipoprotein in atherosclerotic lesions of rabbit and man. J Clin Invest 84:1086–1095

    Article  PubMed  CAS  Google Scholar 

  37. Heinecke JW, Rosen H, Chait A (1984) Iron and copper promote modification of low density lipoprotein by human arterial smooth muscle cells in culture. J Clin Invest 74:1890–1894

    Article  PubMed  CAS  Google Scholar 

  38. Morel DW, DiCorleto PE, Chisolm GM (1984) Endothelial and smooth muscle cells alter low density lipoprotein in vitro by free radical oxidation. Arteriosclerosis 4:357–364

    Article  PubMed  CAS  Google Scholar 

  39. Steinbrecher UP, Parthasarathy S, Leake DS et al (1984) Modification of low density lipoprotein by endothelial cells involves lipid peroxidation and degradation of low density lipoprotein phospholipids. Proc Natl Acad Sci U S A 81:3883–3887

    Article  PubMed  CAS  Google Scholar 

  40. Glass CK, Witztum JL (2001) Atherosclerosis. The road ahead. Cell 104:503–516

    Article  PubMed  CAS  Google Scholar 

  41. Carew TE, Schwenke DC, Steinberg D (1987) Antiatherogenic effect of probucol unrelated to its hypocholesterolemic effect: evidence that antioxidants in vivo can selectively inhibit low density lipoprotein degradation in macrophage-rich fatty streaks and slow the progression of atherosclerosis in the Watanabe heritable hyperlipidemic rabbit. Proc Natl Acad Sci U S A 84:7725–7729

    Article  PubMed  CAS  Google Scholar 

  42. Kita T, Nagano Y, Yokode M et al (1987) Probucol prevents the progression of atherosclerosis in Watanabe heritable hyperlipidemic rabbit, an animal model for familial hypercholesterolemia. Proc Natl Acad Sci U S A 84:5928–5931

    Article  PubMed  CAS  Google Scholar 

  43. Parthasarathy S, Young SG, Witztum JL et al (1986) Probucol inhibits oxidative modification of low density lipoprotein. J Clin Invest 77:641–644

    Article  PubMed  CAS  Google Scholar 

  44. Hunt JV, Dean RT, Wolff SP (1988) Hydroxyl radical production and autoxidative glycosylation. Glucose autoxidation as the cause of protein damage in the experimental glycation model of diabetes mellitus and ageing. Biochem J 256:205–212

    PubMed  CAS  Google Scholar 

  45. Huggins TG, Wells-Knecht MC, Detorie NA et al (1993) Formation of o-tyrosine and dityrosine in proteins during radiolytic and metal-catalyzed oxidation. J Biol Chem 268:12341–12347

    PubMed  CAS  Google Scholar 

  46. Huggins TG, Staton MW, Dyer DG et al (1992) o-Tyrosine and dityrosine concentrations in oxidized proteins and lens proteins with age. Ann N Y Acad Sci 663:436–437

    Article  PubMed  CAS  Google Scholar 

  47. Kaur H, Halliwell B (1994) Detection of hydroxyl radicals by aromatic hydroxylation. Methods Enzymol 233:67–82

    Article  PubMed  CAS  Google Scholar 

  48. Stern DM, Yan SD, Yan SF et al (2002) Receptor for advanced glycation endproducts (RAGE) and the complications of diabetes. Ageing Res Rev 1:1–15

    Article  PubMed  CAS  Google Scholar 

  49. Miyata T, van Ypersele de Strihou C, Kurokawa K et al (1999) Alterations in nonenzymatic biochemistry in uremia: origin and significance of “carbonyl stress” in long-term uremic complications. Kidney Int 55:389–399

    Article  PubMed  CAS  Google Scholar 

  50. Miyata T, Ueda Y, Yoshida A et al (1997) Clearance of pentosidine, an advanced glycation end product, by different modalities of renal replacement therapy. Kidney Int 51:880–887

    Article  PubMed  CAS  Google Scholar 

  51. Miyata T, Fu MX, Kurokawa K et al (1998) Autoxidation products of both carbohydrates and lipids are increased in uremic plasma: is there oxidative stress in uremia? Kidney Int 54:1290–1295

    Article  PubMed  CAS  Google Scholar 

  52. Dyer DG, Blackledge JA, Thorpe SR et al (1991) Formation of pentosidine during nonenzymatic browning of proteins by glucose. Identification of glucose and other carbohydrates as possible precursors of pentosidine in vivo. J Biol Chem 266:11654–11660

    PubMed  CAS  Google Scholar 

  53. McCance DR, Dyer DG, Dunn JA et al (1993) Maillard reaction products and their relation to complications in insulin-dependent diabetes mellitus. J Clin Invest 91:2470–2478

    Article  PubMed  CAS  Google Scholar 

  54. Monnier VM (2001) Transition metals redox: reviving an old plot for diabetic vascular disease. J Clin Invest 107:799–801

    Article  PubMed  CAS  Google Scholar 

  55. Sell DR, Lapolla A, Odetti P et al (1992) Pentosidine formation in skin correlates with severity of complications in individuals with long-standing IDDM. Diabetes 41:1286–1292

    Article  PubMed  CAS  Google Scholar 

  56. Pennathur S, Ido Y, Heller JI et al (2005) Reactive carbonyls and polyunsaturated fatty acids produce a hydroxyl radical-like species: a potential pathway for oxidative damage of retinal proteins in diabetes. J Biol Chem 280:22706–22714

    Article  PubMed  CAS  Google Scholar 

  57. Leeuwenburgh C, Hardy MM, Hazen SL et al (1997) Reactive nitrogen intermediates promote low density lipoprotein oxidation in human atherosclerotic intima. J Biol Chem 272:1433–1436

    Article  PubMed  CAS  Google Scholar 

  58. Leeuwenburgh C, Rasmussen JE, Hsu FF et al (1997) Mass spectrometric quantification of markers for protein oxidation by tyrosyl radical, copper, and hydroxyl radical in low density lipoprotein isolated from human atherosclerotic plaques. J Biol Chem 272:3520–3526

    Article  PubMed  CAS  Google Scholar 

  59. Pennathur S, Bergt C, Shao B et al (2004) Human atherosclerotic intima and blood of patients with established coronary artery disease contain high density lipoprotein damaged by reactive nitrogen species. J Biol Chem 279:42977–42983

    Article  PubMed  CAS  Google Scholar 

  60. Shishehbor MH, Aviles RJ, Brennan ML et al (2003) Association of nitrotyrosine levels with cardiovascular disease and modulation by statin therapy. J Am Med Assoc 289:1675–1680

    Article  CAS  Google Scholar 

  61. Shishehbor MH, Brennan ML, Aviles RJ et al (2003) Statins promote potent systemic antioxidant effects through specific inflammatory pathways. Circulation 108:426–431

    Article  PubMed  CAS  Google Scholar 

  62. Heart Outcomes Prevention Evaluation Study Investigators (2000) Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Lancet 355:253–259

    Article  Google Scholar 

  63. Lambeth JDNOX (2004) Enzymes and the biology of reactive oxygen. Nat Rev Immunol 4:181–189

    Article  PubMed  CAS  Google Scholar 

  64. Rhee SG, Bae YS, Lee SR et al (2000) Hydrogen peroxide: a key messenger that modulates protein phosphorylation through cysteine oxidation. Sci STKE 2000:PE1

    Article  Google Scholar 

  65. Landmesser U, Dikalov S, Price SR et al (2003) Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension. J Clin Invest 111:1201–1209

    PubMed  CAS  Google Scholar 

  66. Vasquez-Vivar J, Kalyanaraman B, Martasek P et al (1998) Superoxide generation by endothelial nitric oxide synthase: the influence of cofactors. Proc Natl Acad Sci U S A 95:9220–9225

    Article  PubMed  CAS  Google Scholar 

  67. Hammes HP, Du X, Edelstein D et al (2003) Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy. Nat Med 9:294–299

    Article  PubMed  CAS  Google Scholar 

  68. Guzik TJ, Sadowski J, Guzik B et al (2006) Coronary artery superoxide production and nox isoform expression in human coronary artery disease. Arterioscler Thromb Vasc Biol 26:333–339

    Article  PubMed  CAS  Google Scholar 

  69. Clark RA, Klebanoff SJ (1977) Myeloperoxidase–H2O2–halide system: cytotoxic effect on human blood leukocytes. Blood 50:65–70

    PubMed  CAS  Google Scholar 

  70. Klebanoff SJ (1980) Oxygen metabolism and the toxic properties of phagocytes. Ann Intern Med 93:480–489

    PubMed  CAS  Google Scholar 

  71. Eiserich JP, Hristova M, Cross CE et al (1998) Formation of nitric oxide-derived inflammatory oxidants by myeloperoxidase in neutrophils. Nature 391:393–397

    Article  PubMed  CAS  Google Scholar 

  72. Gaut JP, Byun J, Tran HD et al (2002) Myeloperoxidase produces nitrating oxidants in vivo. J Clin Invest 109:1311–1319

    PubMed  CAS  Google Scholar 

  73. Ishii H, Jirousek MR, Koya D et al (1996) Amelioration of vascular dysfunctions in diabetic rats by an oral PKC beta inhibitor. Science 272:728–731

    Article  PubMed  CAS  Google Scholar 

  74. King GL, Ishii H, Koya D (1997) Diabetic vascular dysfunctions: a model of excessive activation of protein kinase C. Kidney Int Suppl 60:S77–S85

    PubMed  CAS  Google Scholar 

  75. Bergt C, Pennathur S, Fu X et al (2004) The myeloperoxidase product hypochlorous acid oxidizes HDL in the human artery wall and impairs ABCA1-dependent cholesterol transport. Proc Natl Acad Sci U S A 101:13032–13037

    Article  PubMed  CAS  Google Scholar 

  76. Bhattacharjee S, Pennathur S, Byun J et al (2001) NADPH oxidase of neutrophils elevates o,o’-dityrosine cross-links in proteins and urine during inflammation. Arch Biochem Biophys 395:69–77

    Article  PubMed  CAS  Google Scholar 

  77. Brennan ML, Hazen SL (2003) Amino acid and protein oxidation in cardiovascular disease. Amino Acids 25:365–374

    Article  PubMed  CAS  Google Scholar 

  78. Hazen SL, Crowley JR, Mueller DM et al (1997) Mass spectrometric quantification of 3-chlorotyrosine in human tissues with attomole sensitivity: a sensitive and specific marker for myeloperoxidase-catalyzed chlorination at sites of inflammation. Free Radic Biol Med 23:909–916

    Article  PubMed  CAS  Google Scholar 

  79. Lamharzi N, Renard CB, Kramer F et al (2004) Hyperlipidemia in concert with hyperglycemia stimulates the proliferation of macrophages in atherosclerotic lesions: potential role of glucose-oxidized LDL. Diabetes 53:3217–3225

    Article  PubMed  CAS  Google Scholar 

  80. Leeuwenburgh C, Hansen P, Shaish A et al (1998) Markers of protein oxidation by hydroxyl radical and reactive nitrogen species in tissues of aging rats. Am J Physiol 274:R453–R461

    PubMed  CAS  Google Scholar 

  81. Leeuwenburgh C, Hansen PA, Holloszy JO et al (1999) Hydroxyl radical generation during exercise increases mitochondrial protein oxidation and levels of urinary dityrosine. Free Radic Biol Med 27:186–192

    Article  PubMed  CAS  Google Scholar 

  82. Leeuwenburgh C, Wagner P, Holloszy JO et al (1997) Caloric restriction attenuates dityrosine cross-linking of cardiac and skeletal muscle proteins in aging mice. Arch Biochem Biophys 346:74–80

    Article  PubMed  CAS  Google Scholar 

  83. Pennathur S, Heinecke JW (2004) Mechanisms of oxidative stress in diabetes: implications for the pathogenesis of vascular disease and antioxidant therapy. Front Biosci 9:565–574

    Article  PubMed  CAS  Google Scholar 

  84. Pennathur S, Jackson-Lewis V, Przedborski S et al (1999) Mass spectrometric quantification of 3-nitrotyrosine, ortho-tyrosine, and o,o’-dityrosine in brain tissue of 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine-treated mice, a model of oxidative stress in Parkinson’s disease. J Biol Chem 274:34621–34628

    Article  PubMed  CAS  Google Scholar 

  85. Pennathur S, Wagner JD, Leeuwenburgh C et al (2001) A hydroxyl radical-like species oxidizes cynomolgus monkey artery wall proteins in early diabetic vascular disease. J Clin Invest 107:853–860

    Article  PubMed  CAS  Google Scholar 

  86. Zheng L, Nukuna B, Brennan ML et al (2004) Apolipoprotein A-I is a selective target for myeloperoxidase-catalyzed oxidation and functional impairment in subjects with cardiovascular disease. J Clin Invest 114:529–541

    PubMed  CAS  Google Scholar 

  87. Leeuwenburgh C, Hansen PA, Holloszy JO et al (1999) Oxidized amino acids in the urine of aging rats: potential markers for assessing oxidative stress in vivo. Am J Physiol 276:R128–R135

    PubMed  CAS  Google Scholar 

  88. Abu-Soud HM, Hazen SL (2000) Nitric oxide is a physiological substrate for mammalian peroxidases. J Biol Chem 275:37524–37532

    Article  PubMed  CAS  Google Scholar 

  89. Beckman JS, Chen J, Ischiropoulos H et al (1994) Oxidative chemistry of peroxynitrite. Methods Enzymol 233:229–240

    Article  PubMed  CAS  Google Scholar 

  90. Brennan ML, Hazen SL (2003) Emerging role of myeloperoxidase and oxidant stress markers in cardiovascular risk assessment. Curr Opin Lipidol 14:353–359

    Article  PubMed  CAS  Google Scholar 

  91. Heinecke JW (2002) Oxidized amino acids: culprits in human atherosclerosis and indicators of oxidative stress. Free Radic Biol Med 32:1090–1101

    Article  PubMed  CAS  Google Scholar 

  92. Giulivi C, Traaseth NJ, Davies KJ (2003) Tyrosine oxidation products: analysis and biological relevance. Amino Acids 25:227–232

    Article  PubMed  CAS  Google Scholar 

  93. DiMarco T, Giulivi C (2007) Current analytical methods for the detection of dityrosine, a biomarker of oxidative stress, in biological samples. Mass Spectrom Rev 26:108–120

    Article  PubMed  CAS  Google Scholar 

  94. Witze ES, Old WM, Resing KA et al (2007) Mapping protein post-translational modifications with mass spectrometry. Nat Methods 4:798–806

    Article  PubMed  CAS  Google Scholar 

  95. Schoneich C, Sharov VS (2006) Mass spectrometry of protein modifications by reactive oxygen and nitrogen species. Free Radic Biol Med 41:1507–1520

    Article  PubMed  CAS  Google Scholar 

  96. Shishehbor MH, Hazen SL (2004) Inflammatory and oxidative markers in atherosclerosis: relationship to outcome. Curr Atheroscler Rep 6:243–250

    Article  PubMed  Google Scholar 

  97. Thannickal VJ, Loyd JE (2008) Idiopathic pulmonary fibrosis: a disorder of lung regeneration? Am J Respir Crit Care Med 178:663–665

    Article  PubMed  Google Scholar 

  98. Gurtner GC, Werner S, Barrandon Y et al (2008) Wound repair and regeneration. Nature 453:314–321

    Article  PubMed  CAS  Google Scholar 

  99. Urtasun R, de la Rosa LC, Nieto N (2008) Oxidative and nitrosative stress and fibrogenic response. Clin Liver Dis 12:769–790

    Article  PubMed  CAS  Google Scholar 

  100. Zhao W, Zhao T, Chen Y et al (2008) Oxidative stress mediates cardiac fibrosis by enhancing transforming growth factor-beta1 in hypertensive rats. Mol Cell Biochem 317:43–50

    Article  PubMed  CAS  Google Scholar 

  101. Kinnula VL, Fattman CL, Tan RJ et al (2005) Oxidative stress in pulmonary fibrosis: a possible role for redox modulatory therapy. Am J Respir Crit Care Med 172:417–422

    Article  PubMed  Google Scholar 

  102. Cave AC, Brewer AC, Narayanapanicker A et al (2006) NADPH oxidases in cardiovascular health and disease. Antioxid Redox Signal 8:691–728

    Article  PubMed  CAS  Google Scholar 

  103. Murdoch CE, Grieve DJ, Cave AC et al (2006) NADPH oxidase and heart failure. Curr Opin Pharmacol 6:148–153

    Article  PubMed  CAS  Google Scholar 

  104. Heymes C, Bendall JK, Ratajczak P et al (2003) Increased myocardial NADPH oxidase activity in human heart failure. J Am Coll Cardiol 41:2164–2171

    Article  PubMed  CAS  Google Scholar 

  105. Maack C, Kartes T, Kilter H et al (2003) Oxygen free radical release in human failing myocardium is associated with increased activity of rac1-GTPase and represents a target for statin treatment. Circulation 108:1567–1574

    Article  PubMed  CAS  Google Scholar 

  106. Li JM, Gall NP, Grieve DJ et al (2002) Activation of NADPH oxidase during progression of cardiac hypertrophy to failure. Hypertension 40:477–484

    Article  PubMed  CAS  Google Scholar 

  107. Park YM, Park MY, Suh YL et al (2004) NAD(P)H oxidase inhibitor prevents blood pressure elevation and cardiovascular hypertrophy in aldosterone-infused rats. Biochem Biophys Res Commun 313:812–817

    Article  PubMed  CAS  Google Scholar 

  108. Stas S, Whaley-Connell A, Habibi J et al (2007) Mineralocorticoid receptor blockade attenuates chronic overexpression of the renin-angiotensin-aldosterone system stimulation of reduced nicotinamide adenine dinucleotide phosphate oxidase and cardiac remodeling. Endocrinology 148:3773–3780

    Article  PubMed  CAS  Google Scholar 

  109. Johar S, Cave AC, Narayanapanicker A et al (2006) Aldosterone mediates angiotensin II-induced interstitial cardiac fibrosis via a Nox2-containing NADPH oxidase. FASEB J 20:1546–1548

    Article  PubMed  CAS  Google Scholar 

  110. Looi YH, Grieve DJ, Siva A et al (2008) Involvement of Nox2 NADPH oxidase in adverse cardiac remodeling after myocardial infarction. Hypertension 51:319–325

    Article  PubMed  CAS  Google Scholar 

  111. Grieve DJ, Byrne JA, Siva A et al (2006) Involvement of the nicotinamide adenosine dinucleotide phosphate oxidase isoform Nox2 in cardiac contractile dysfunction occurring in response to pressure overload. J Am Coll Cardiol 47:817–826

    Article  PubMed  CAS  Google Scholar 

  112. Hinz B, Phan SH, Thannickal VJ et al (2007) The myofibroblast: one function, multiple origins. Am J Pathol 170:1807–1816

    Article  PubMed  CAS  Google Scholar 

  113. Cucoranu I, Clempus R, Dikalova A et al (2005) NAD(P)H oxidase 4 mediates transforming growth factor-beta1-induced differentiation of cardiac fibroblasts into myofibroblasts. Circ Res 97:900–907

    Article  PubMed  CAS  Google Scholar 

  114. Spurney CF, Knoblach S, Pistilli EE et al (2008) Dystrophin-deficient cardiomyopathy in mouse: expression of Nox4 and Lox are associated with fibrosis and altered functional parameters in the heart. Neuromuscul Disord 18:371–381

    Article  PubMed  Google Scholar 

  115. Heinecke JW (2001) Is the emperor wearing clothes? Clinical trials of vitamin E and the LDL oxidation hypothesis. Arterioscler Thromb Vasc Biol 21:1261–1264

    Article  PubMed  CAS  Google Scholar 

  116. Meagher EA, Barry OP, Lawson JA et al (2001) Effects of vitamin E on lipid peroxidation in healthy persons. J Am Med Assoc 285:1178–1182

    Article  CAS  Google Scholar 

  117. Mashima R, Witting PK, Stocker R (2001) Oxidants and antioxidants in atherosclerosis. Curr Opin Lipidol 12:411–418

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Research in the authors’ laboratory is supported by grants from the National Institutes of Health, R01 HL094230 (SP and VJT), R21 HL092237 (SP) and R01 HL067967 (VJT), the Michigan Metabolomics and Obesity Center, and the Biomedical Mass Spectrometry Facility, University of Michigan. SP is supported by the Doris Duke Foundation Clinical Scientist Development Award.

Author information

Authors and Affiliations

  1. Division of Nephrology, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, 48109, USA

    Subramaniam Pennathur

  2. Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, 48109, USA

    Louise Hecker

  3. Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA

    Victor J. Thannickal

  4. Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, 48109, USA

    Victor J. Thannickal

Authors
  1. Subramaniam Pennathur
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Louise Hecker
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Victor J. Thannickal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Victor J. Thannickal .

Editor information

Editors and Affiliations

  1. Physiologisches Institut, Universität Gießen, Aulweg 129, Gießen, 35392, Germany

    Heinrich Sauer

  2. James Black Centre, King's College, London, Coldharbour Lane 125, London, SE5 9NU, United Kingdom

    Ajay M. Shah

  3. Fac. Medicina, Instituto do Coração (INCOR), Universidade de São Paulo, Av. Enéas de Carvalho Aguiar 44, São Paulo, 05403-000, São Paulo, Brazil

    Francisco R. M. Laurindo

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Pennathur, S., Hecker, L., Thannickal, V.J. (2010). Oxidative Stress and Cardiovascular Fibrosis. In: Sauer, H., Shah, A., Laurindo, F. (eds) Studies on Cardiovascular Disorders. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-600-9_22

Download citation

Publish with us

Policies and ethics

Search

Navigation