Skip to main content

Modulation of Oxidative Stress in Cardiovascular Diseases

  • Chapter
  • First Online:
Modulation of Oxidative Stress in Heart Disease

Abstract

Cardiovascular disease (CVD), the leading cause of morbidity and mortality, represents a major global health and economic burden worldwide [1, 2]. The World Health Organization report has projected that approximately half of all deaths in developed countries will be due to CVD by 2020. CVD is a multifactorial disorder, which encompasses a broad range of injuries of the vasculature and heart including atherosclerosis, coronary heart disease leading to myocardial infarction, peripheral vascular disease, stroke, aneurysms, and cardiomyopathy [3–6] (Fig. 10.1). There is no single cause for CVD, but there are a range of risk factors, which increase the likelihood for clinical manifestations of cardiovascular disease. These risk factors for CVD include obesity, dyslipidemia, diabetes, hypertension, smoking, and aging as well as a positive family history and environmental factors [5, 7–9]. A significant number of studies have shown a close association among these cardiovascular risk factors. Indeed, hypertension, dyslipidemia, obesity, insulin resistance, and chronic hyperglycemia often coexist and synergistically enhance the risk for CVD-related deaths [1, 5, 7, 8]. Reports suggest that diabetes increases the risk of stroke and myocardial infarction with diabetic patients demonstrating a 1.7 times higher risk of CVD death than nondiabetic individuals [1]. In addition, the risk for CVD including coronary disease and stroke is elevated with a rise in blood pressure [8, 10]. Smoking is an avoidable risk factor of CVD, and a person’s risk of CVD mortality can be reduced by 36% over 2 years upon cessation of smoking [11]. The burden of CVD risk increases with age and can be decreased partly by modifying and monitoring other coexisting CVD risk factors [12]. CVD can also result from environmental and demographic factors. The high prevalence of CVD and its risk factors among the general population have motivated research investigating the pathological mechanisms of CVD and to develop novel approaches to prevent the progression of this disease. This has led to a better understanding of the underlying pathogenic mechanisms for the development and progression of CVD.

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

Access this chapter

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 219.99
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. Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R et al (2017) Heart disease and stroke statistics-2017 update: a report from the American Heart Association. Circulation 135(10):e146–e603

    Article  PubMed  PubMed Central  Google Scholar 

  2. Collaborators GBDRF (2018) Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017: a systematic analysis for the global burden of disease study 2017. Lancet 392(10159):1923–1994

    Article  Google Scholar 

  3. Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M (1998) Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 339(4):229–234

    Article  CAS  PubMed  Google Scholar 

  4. Reaven GM, Chen YD (1996) Insulin resistance, its consequences, and coronary heart disease. Must we choose one culprit? Circulation 93(10):1780–1783

    Article  CAS  PubMed  Google Scholar 

  5. Reaven GM, Lithell H, Landsberg L (1996) Hypertension and associated metabolic abnormalities–the role of insulin resistance and the sympathoadrenal system. N Engl J Med 334(6):374–381

    Article  CAS  PubMed  Google Scholar 

  6. Selby JV, Newman B, Quiroga J, Christian JC, Austin MA, Fabsitz RR (1991) Concordance for dyslipidemic hypertension in male twins. JAMA 265(16):2079–2084

    Article  CAS  PubMed  Google Scholar 

  7. Haffner SM (1998) Epidemiology of type 2 diabetes: risk factors. Diabetes Care 21(Suppl 3):C3–C6

    Article  PubMed  Google Scholar 

  8. Oparil S, Zaman MA, Calhoun DA (2003) Pathogenesis of hypertension. Ann Intern Med 139(9):761–776

    Article  CAS  PubMed  Google Scholar 

  9. Reed T, Quiroga J, Selby JV, Carmelli D, Christian JC, Fabsitz RR et al (1991) Concordance of ischemic heart disease in the NHLBI twin study after 14–18 years of follow-up. J Clin Epidemiol 44(8):797–805

    Article  CAS  PubMed  Google Scholar 

  10. Dinesh Shah A, Langenberg C, Rapsomaniki E, Denaxas S, Pujades-Rodriguez M, Gale CP et al (2015) Type 2 diabetes and incidence of a wide range of cardiovascular diseases: a cohort study in 1.9 million people. Lancet 385(Suppl 1):S86

    Article  PubMed  Google Scholar 

  11. Rigotti NA, Clair C (2013) Managing tobacco use: the neglected cardiovascular disease risk factor. Eur Heart J 34(42):3259–3267

    Article  PubMed  Google Scholar 

  12. Dhingra R, Vasan RS (2012) Age as a risk factor. Med Clin North Am 96(1):87–91

    Article  PubMed  Google Scholar 

  13. Panth N, Paudel KR, Parajuli K (2016) Reactive oxygen species: a key hallmark of cardiovascular disease. Adv Med 2016:9152732

    Article  PubMed  PubMed Central  Google Scholar 

  14. Droge W (2002) Free radicals in the physiological control of cell function. Physiol Rev 82(1):47–95

    Article  CAS  PubMed  Google Scholar 

  15. He F, Zuo L (2015) Redox roles of reactive oxygen species in cardiovascular diseases. Int J Mol Sci 16(11):27770–27780

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Jha JC, Banal C, Chow BS, Cooper ME, Jandeleit-Dahm K (2016) Diabetes and kidney disease: role of oxidative stress. Antioxid Redox Signal 25(12):657–684

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Taverne YJ, Bogers AJ, Duncker DJ, Merkus D (2013) Reactive oxygen species and the cardiovascular system. Oxidative Med Cell Longev 2013:862423

    Article  CAS  Google Scholar 

  18. Jha JC, Watson AMD, Mathew G, de Vos LC, Jandeleit-Dahm K (2017) The emerging role of NADPH oxidase NOX5 in vascular disease. Clin Sci 131(10):981–990

    Article  CAS  Google Scholar 

  19. Paravicini TM, Touyz RM (2008) NADPH oxidases, reactive oxygen species, and hypertension: clinical implications and therapeutic possibilities. Diabetes Care 31(Suppl 2):S170–S180

    Article  CAS  PubMed  Google Scholar 

  20. Galano A, Castaneda-Arriaga R, Perez-Gonzalez A, Tan DX, Reiter RJ (2016) Phenolic melatonin-related compounds: their role as chemical protectors against oxidative stress. Molecules 21(11):1442

    Article  PubMed Central  CAS  Google Scholar 

  21. Jha JC, Ho F, Dan C, Jandeleit-Dahm K (2018) A causal link between oxidative stress and inflammation in cardiovascular and renal complications of diabetes. Clin Sci 132(16):1811–1836

    Article  CAS  Google Scholar 

  22. Akbar S, Bellary S, Griffiths HR (2011) Dietary antioxidant interventions in type 2 diabetes patients: a meta-analysis. Br J Diab Vasc Dis 11(2):62–68

    Article  CAS  Google Scholar 

  23. Kaspar JW, Niture SK, Jaiswal AK (2009) Nrf2:INrf2 (Keap1) signaling in oxidative stress. Free Radic Biol Med 47(9):1304–1309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kensler TW, Wakabayashi N, Biswal S (2007) Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu Rev Pharmacol Toxicol 47:89–116

    Article  CAS  PubMed  Google Scholar 

  25. Chan K, Kan YW (1999) Nrf2 is essential for protection against acute pulmonary injury in mice. Proc Natl Acad Sci U S A 96(22):12731–12736

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Thimmulappa RK, Lee H, Rangasamy T, Reddy SP, Yamamoto M, Kensler TW et al (2006) Nrf2 is a critical regulator of the innate immune response and survival during experimental sepsis. J Clin Invest 116(4):984–995

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kovac S, Angelova PR, Holmström KM, Zhang Y, Dinkova-Kostova AT, Abramov AY (2015) Nrf2 regulates ROS production by mitochondria and NADPH oxidase. Biochim Biophys Acta Gen Subj 1850(4):794–801

    Article  CAS  Google Scholar 

  28. Zhu H, Jia Z, Misra BR, Zhang L, Cao Z, Yamamoto M et al (2008) Nuclear factor E2-related factor 2-dependent myocardiac cytoprotection against oxidative and electrophilic stress. Cardiovasc Toxicol 8(2):71–85

    Article  CAS  PubMed  Google Scholar 

  29. Chen LH, Huang Q, Wan L, Zeng LY, Li SF, Li YP et al (2006) Expression, purification, and in vitro refolding of a humanized single-chain Fv antibody against human CTLA4 (CD152). Protein Expr Purif 46(2):495–502

    Article  CAS  PubMed  Google Scholar 

  30. Reuland DJ, McCord JM, Hamilton KL (2013) The role of Nrf2 in the attenuation of cardiovascular disease. Exerc Sport Sci Rev 41(3):162–168

    Article  PubMed  Google Scholar 

  31. Donovan EL, McCord JM, Reuland DJ, Miller BF, Hamilton KL (2012) Phytochemical activation of Nrf2 protects human coronary artery endothelial cells against an oxidative challenge. Oxidative Med Cell Longev 2012:132931

    Article  CAS  Google Scholar 

  32. Sharma A, Rizky L, Stefanovic N, Tate M, Ritchie RH, Ward KW et al (2017) The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activator dh404 protects against diabetes-induced endothelial dysfunction. Cardiovasc Diabetol 16(1):33

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Tan SM, Sharma A, Stefanovic N, Yuen DY, Karagiannis TC, Meyer C et al (2014) Derivative of bardoxolone methyl, dh404, in an inverse dose-dependent manner lessens diabetes-associated atherosclerosis and improves diabetic kidney disease. Diabetes 63(9):3091–3103

    Article  PubMed  Google Scholar 

  34. Pergola PE, Krauth M, Huff JW, Ferguson DA, Ruiz S, Meyer CJ et al (2011) Effect of bardoxolone methyl on kidney function in patients with T2D and stage 3b-4 CKD. Am J Nephrol 33(5):469–476

    Article  CAS  PubMed  Google Scholar 

  35. Pergola PE, Raskin P, Toto RD, Meyer CJ, Huff JW, Grossman EB et al (2011) Bardoxolone methyl and kidney function in CKD with type 2 diabetes. N Engl J Med 365(4):327–336

    Article  CAS  PubMed  Google Scholar 

  36. Bai Y, Cui W, Xin Y, Miao X, Barati MT, Zhang C et al (2013) Prevention by sulforaphane of diabetic cardiomyopathy is associated with up-regulation of Nrf2 expression and transcription activation. J Mol Cell Cardiol 57:82–95

    Article  CAS  PubMed  Google Scholar 

  37. Miao X, Cui W, Sun W, Xin Y, Wang B, Tan Y et al (2013) Therapeutic effect of MG132 on the aortic oxidative damage and inflammatory response in OVE26 type 1 diabetic mice. Oxidative Med Cell Longev 2013:879516

    Article  CAS  Google Scholar 

  38. Wang Y, Zhang Z, Sun W, Tan Y, Liu Y, Zheng Y et al (2014) Sulforaphane attenuation of type 2 diabetes-induced aortic damage was associated with the upregulation of Nrf2 expression and function. Oxidative Med Cell Longev 2014:123963

    Google Scholar 

  39. Howden R (2013) Nrf2 and cardiovascular defense. Oxidative Med Cell Longev 2013:104308

    Google Scholar 

  40. Mann GE, Bonacasa B, Ishii T, Siow RC (2009) Targeting the redox sensitive Nrf2-Keap1 defense pathway in cardiovascular disease: protection afforded by dietary isoflavones. Curr Opin Pharmacol 9(2):139–145

    Article  CAS  PubMed  Google Scholar 

  41. El-Demerdash E, Awad AS, Taha RM, El-Hady AM, Sayed-Ahmed MM (2005) Probucol attenuates oxidative stress and energy decline in isoproterenol-induced heart failure in rat. Pharmacol Res 51(4):311–318

    Article  CAS  PubMed  Google Scholar 

  42. Tardif JC, Gregoire J, Schwartz L, Title L, Laramee L, Reeves F et al (2003) Effects of AGI-1067 and probucol after percutaneous coronary interventions. Circulation 107(4):552–558

    Article  CAS  PubMed  Google Scholar 

  43. Tardif JC, McMurray JJ, Klug E, Small R, Schumi J, Choi J et al (2008) Effects of succinobucol (AGI-1067) after an acute coronary syndrome: a randomised, double-blind, placebo-controlled trial. Lancet 371(9626):1761–1768

    Article  CAS  PubMed  Google Scholar 

  44. Li S, Liang J, Niimi M, Bilal Waqar A, Kang D, Koike T et al (2014) Probucol suppresses macrophage infiltration and MMP expression in atherosclerotic plaques of WHHL rabbits. J Atheroscler Thromb 21(7):648–658

    Article  CAS  PubMed  Google Scholar 

  45. Sundell CL, Somers PK, Meng CQ, Hoong LK, Suen KL, Hill RR et al (2003) AGI-1067: a multifunctional phenolic antioxidant, lipid modulator, anti-inflammatory and antiatherosclerotic agent. J Pharmacol Exp Ther 305(3):1116–1123

    Article  CAS  PubMed  Google Scholar 

  46. Tardif JC, Gregoire J, L'Allier PL, Ibrahim R, Anderson TJ, Reeves F et al (2008) Effects of the antioxidant succinobucol (AGI-1067) on human atherosclerosis in a randomized clinical trial. Atherosclerosis 197(1):480–486

    Article  CAS  PubMed  Google Scholar 

  47. Li L, Guo J, Wang Y, Xiong X, Tao H, Li J et al (2018) A broad-spectrum ROS-eliminating material for prevention of inflammation and drug-induced organ toxicity. Adv Sci (Weinh) 5(10):1800781

    Article  CAS  Google Scholar 

  48. Wang Y, Li L, Zhao W, Dou Y, An H, Tao H et al (2018) Targeted therapy of atherosclerosis by a broad-spectrum reactive oxygen species scavenging nanoparticle with intrinsic anti-inflammatory activity. ACS Nano 12(9):8943–8960

    Article  CAS  PubMed  Google Scholar 

  49. Jha JC, Banal C, Okabe J, Gray SP, Hettige T, Chow BSM et al (2017) NADPH oxidase Nox5 accelerates renal injury in diabetic nephropathy. Diabetes 66(10):2691–2703

    Article  CAS  PubMed  Google Scholar 

  50. Jha JC, Gray SP, Barit D, Okabe J, El-Osta A, Namikoshi T et al (2014) Genetic targeting or pharmacologic inhibition of NADPH oxidase nox4 provides renoprotection in long-term diabetic nephropathy. J Am Soc Nephrol 25(6):1237–1254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Gray SP, Di Marco E, Kennedy K, Chew P, Okabe J, El-Osta A et al (2016) Reactive oxygen species can provide atheroprotection via NOX4-dependent inhibition of inflammation and vascular remodeling. Arterioscler Thromb Vasc Biol 36(2):295–307

    Article  CAS  PubMed  Google Scholar 

  52. Gray SP, Di Marco E, Okabe J, Szyndralewiez C, Heitz F, Montezano AC et al (2013) NADPH oxidase 1 plays a key role in diabetes mellitus-accelerated atherosclerosis. Circulation 127(18):1888–1902

    Article  CAS  PubMed  Google Scholar 

  53. Sirker A, Zhang M, Shah AM (2011) NADPH oxidases in cardiovascular disease: insights from in vivo models and clinical studies. Basic Res Cardiol 106(5):735–747

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Di Marco E, Gray SP, Chew P, Kennedy K, Cooper ME, Schmidt HH et al (2016) Differential effects of NOX4 and NOX1 on immune cell-mediated inflammation in the aortic sinus of diabetic ApoE−/− mice. Clin Sci 130(15):1363–1374

    Article  CAS  Google Scholar 

  55. Dikalov SI, Dikalova AE, Bikineyeva AT, Schmidt HH, Harrison DG, Griendling KK (2008) Distinct roles of Nox1 and Nox4 in basal and angiotensin II-stimulated superoxide and hydrogen peroxide production. Free Radic Biol Med 45(9):1340–1351

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Martyn KD, Frederick LM, von Loehneysen K, Dinauer MC, Knaus UG (2006) Functional analysis of Nox4 reveals unique characteristics compared to other NADPH oxidases. Cell Signal 18(1):69–82

    Article  CAS  PubMed  Google Scholar 

  57. Amann B, Tinzmann R, Angelkort B (2003) ACE inhibitors improve diabetic nephropathy through suppression of renal MCP-1. Diabetes Care 26(8):2421–2425

    Article  CAS  PubMed  Google Scholar 

  58. Borchi E, Bargelli V, Stillitano F, Giordano C, Sebastiani M, Nassi PA et al (2010) Enhanced ROS production by NADPH oxidase is correlated to changes in antioxidant enzyme activity in human heart failure. Biochim Biophys Acta 1802(3):331–338

    Article  CAS  PubMed  Google Scholar 

  59. Johar S, Cave AC, Narayanapanicker A, Grieve DJ, Shah AM (2006) Aldosterone mediates angiotensin II-induced interstitial cardiac fibrosis via a Nox2-containing NADPH oxidase. FASEB J: official publication of the Federation of American Societies for Experimental Biology 20(9):1546–1548

    Article  CAS  Google Scholar 

  60. Kuroda J, Ago T, Matsushima S, Zhai P, Schneider MD, Sadoshima J (2010) NADPH oxidase 4 (Nox4) is a major source of oxidative stress in the failing heart. Proc Natl Acad Sci U S A 107(35):15565–15570

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Kuroda J, Sadoshima J (2010) NADPH oxidase and cardiac failure. J Cardiovasc Transl Res 3(4):314–320

    Article  PubMed  PubMed Central  Google Scholar 

  62. Stevenson MD, Canugovi C, Vendrov AE, Hayami T, Bowles DE, Krause KH et al (2018) NADPH oxidase 4 regulates inflammation in ischemic heart failure: role of soluble epoxide hydrolase. Antioxid Redox Signal

    Google Scholar 

  63. Gray SP, Jha JC, Kennedy K, van Bommel E, Chew P, Szyndralewiez C et al (2017) Combined NOX1/4 inhibition with GKT137831 in mice provides dose-dependent Reno- and atheroprotection even in established micro- and macrovascular disease. Diabetologia 60(5):927–937

    Article  CAS  PubMed  Google Scholar 

  64. Susztak K, Raff AC, Schiffer M, Böttinger EP (2006) Glucose-induced reactive oxygen species cause apoptosis of podocytes and podocyte depletion at the onset of diabetic nephropathy. Diabetes 55(1):225–233

    Article  CAS  PubMed  Google Scholar 

  65. Ding Y, Chen ZJ, Liu S, Che D, Vetter M, Chang CH (2005) Inhibition of Nox-4 activity by plumbagin, a plant-derived bioactive naphthoquinone. J Pharm Pharmacol 57(1):111–116

    Article  CAS  PubMed  Google Scholar 

  66. Anvari E, Wikstrom P, Walum E, Welsh N (2015) The novel NADPH oxidase 4 inhibitor GLX351322 counteracts glucose intolerance in high-fat diet-treated C57BL/6 mice. Free Radic Res 49(11):1308–1318

    Article  CAS  PubMed  Google Scholar 

  67. Zhou G, Wang Y, He P, Li D (2013) Probucol inhibited Nox2 expression and attenuated podocyte injury in type 2 diabetic nephropathy of db/db mice. Biol Pharm Bull 36(12):1883–1890

    Article  CAS  PubMed  Google Scholar 

  68. Gaggini F, Laleu B, Orchard M, Fioraso-Cartier L, Cagnon L, Houngninou-Molango S et al (2011) Design, synthesis and biological activity of original pyrazolo-pyrido-diazepine, -pyrazine and -oxazine dione derivatives as novel dual Nox4/Nox1 inhibitors. Bioorg Med Chem 19(23):6989–6999

    Article  CAS  PubMed  Google Scholar 

  69. Sedeek M, Callera G, Montezano A, Gutsol A, Heitz F, Szyndralewiez C et al (2010) Critical role of Nox4-based NADPH oxidase in glucose-induced oxidative stress in the kidney: implications in type 2 diabetic nephropathy. Am J Physiol Ren Physiol 299(6):F1348–F1358

    Article  CAS  Google Scholar 

  70. Laleu B, Gaggini F, Orchard M, Fioraso-Cartier L, Cagnon L, Houngninou-Molango S et al (2010) First in class, potent, and orally bioavailable NADPH oxidase isoform 4 (Nox4) inhibitors for the treatment of idiopathic pulmonary fibrosis. J Med Chem 53(21):7715–7730

    Article  CAS  PubMed  Google Scholar 

  71. Aoyama T, Paik YH, Watanabe S, Laleu B, Gaggini F, Fioraso-Cartier L et al (2012) Nicotinamide adenine dinucleotide phosphate oxidase in experimental liver fibrosis: GKT137831 as a novel potential therapeutic agent. Hepatology 56(6):2316–2327

    Article  CAS  PubMed  Google Scholar 

  72. Sedeek M, Gutsol A, Montezano AC, Burger D, Cat AND, Kennedy CR et al (2013) Renoprotective effects of a novel Nox1/4 inhibitor in a mouse model of type 2 diabetes. Clin Sci 124(3):191–202

    Article  CAS  Google Scholar 

  73. Vendrov AE, Hakim ZS, Madamanchi NR, Rojas M, Madamanchi C, Runge MS (2007) Atherosclerosis is attenuated by limiting superoxide generation in both macrophages and vessel wall cells. Arterioscler Thromb Vasc Biol 27(12):2714–2721

    Article  CAS  PubMed  Google Scholar 

  74. Vendrov AE, Madamanchi NR, Niu XL, Molnar KC, Runge M, Szyndralewiez C et al (2010) NADPH oxidases regulate CD44 and hyaluronic acid expression in thrombin-treated vascular smooth muscle cells and in atherosclerosis. J Biol Chem 285(34):26545–26557

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Gorin Y, Cavaglieri RC, Khazim K, Lee DY, Bruno F, Thakur S et al (2015) Targeting NADPH oxidase with a novel dual Nox1/Nox4 inhibitor attenuates renal pathology in type 1 diabetes. Am J Physiol Ren Physiol 308(11):F1276–F1287

    Article  CAS  Google Scholar 

  76. You YH, Quach T, Saito R, Pham J, Sharma K (2016) Metabolomics reveals a key role for fumarate in mediating the effects of NADPH oxidase 4 in diabetic kidney disease. J Am Soc Nephrol: JASN 27(2):466–481

    Article  CAS  PubMed  Google Scholar 

  77. Jarasch ED, Grund C, Bruder G, Heid HW, Keenan TW, Franke WW (1981) Localization of xanthine oxidase in mammary-gland epithelium and capillary endothelium. Cell 25(1):67–82

    Article  CAS  PubMed  Google Scholar 

  78. Harrison R (2002) Structure and function of xanthine oxidoreductase: where are we now? Free Radic Biol Med 33(6):774–797

    Article  CAS  PubMed  Google Scholar 

  79. Pacher P, Nivorozhkin A, Szabo C (2006) Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol. Pharmacol Rev 58(1):87–114

    Article  CAS  PubMed  Google Scholar 

  80. McNally JS, Davis ME, Giddens DP, Saha A, Hwang J, Dikalov S et al (2003) Role of xanthine oxidoreductase and NAD(P)H oxidase in endothelial superoxide production in response to oscillatory shear stress. Am J Physiol Heart Circ Physiol 285(6):H2290–H2297

    Article  CAS  PubMed  Google Scholar 

  81. Zdrenghea M, Sitar-Taut A, Cismaru G, Zdrenghea D, Pop D (2017) Xanthine oxidase inhibitors in ischaemic heart disease. Cardiovasc J Afr 28(3):201–204

    Article  PubMed  PubMed Central  Google Scholar 

  82. Kang SM, Lim S, Song H, Chang W, Lee S, Bae SM et al (2006) Allopurinol modulates reactive oxygen species generation and Ca2+ overload in ischemia-reperfused heart and hypoxia-reoxygenated cardiomyocytes. Eur J Pharmacol 535(1–3):212–219

    Article  CAS  PubMed  Google Scholar 

  83. Goicoechea M, Garcia de Vinuesa S, Verdalles U, Verde E, Macias N, Santos A et al (2015) Allopurinol and progression of CKD and cardiovascular events: long-term follow-up of a randomized clinical trial. Am J Kidney Dis: The Official Journal of the National Kidney Foundation 65(4):543–549

    Article  CAS  Google Scholar 

  84. Singh JA, Ramachandaran R, Yu S, Curtis JR (2017) Allopurinol use and the risk of acute cardiovascular events in patients with gout and diabetes. BMC Cardiovasc Disord 17(1):76

    Article  PubMed  PubMed Central  Google Scholar 

  85. Yisireyili M, Hayashi M, Wu H, Uchida Y, Yamamoto K, Kikuchi R et al (2017) Xanthine oxidase inhibition by febuxostat attenuates stress-induced hyperuricemia, glucose dysmetabolism, and prothrombotic state in mice. Sci Rep 7(1):1266

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  86. White WB, Gunawardhana L (2018) Cardiovascular safety of febuxostat. N Engl J Med 379(16):1584

    PubMed  Google Scholar 

  87. White WB, Saag KG, Becker MA, Borer JS, Gorelick PB, Whelton A et al (2018) Cardiovascular safety of febuxostat or allopurinol in patients with gout. N Engl J Med 378(13):1200–1210

    Article  CAS  PubMed  Google Scholar 

  88. Lytvyn Y, Har R, Locke A, Lai V, Fong D, Advani A et al (2017) Renal and vascular effects of uric acid lowering in normouricemic patients with uncomplicated type 1 diabetes. Diabetes 66(7):1939–1949

    Article  CAS  PubMed  Google Scholar 

  89. Brash AR (1999) Lipoxygenases: occurrence, functions, catalysis, and acquisition of substrate. J Biol Chem 274(34):23679–23682

    Article  CAS  PubMed  Google Scholar 

  90. Kuhn H, Heydeck D, Hugou I, Gniwotta C (1997) In vivo action of 15-lipoxygenase in early stages of human atherogenesis. J Clin Invest 99(5):888–893

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Shappell SB, Boeglin WE, Olson SJ, Kasper S, Brash AR (1999) 15-lipoxygenase-2 (15-LOX-2) is expressed in benign prostatic epithelium and reduced in prostate adenocarcinoma. Am J Pathol 155(1):235–245

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Cyrus T, Pratico D, Zhao L, Witztum JL, Rader DJ, Rokach J et al (2001) Absence of 12/15-lipoxygenase expression decreases lipid peroxidation and atherogenesis in apolipoprotein e-deficient mice. Circulation 103(18):2277–2282

    Article  CAS  PubMed  Google Scholar 

  93. Funk CD, Cyrus T (2001) 12/15-lipoxygenase, oxidative modification of LDL and atherogenesis. Trends Cardiovasc Med 11(3–4):116–124

    CAS  PubMed  Google Scholar 

  94. George J, Afek A, Shaish A, Levkovitz H, Bloom N, Cyrus T et al (2001) 12/15-lipoxygenase gene disruption attenuates atherogenesis in LDL receptor-deficient mice. Circulation 104(14):1646–1650

    Article  CAS  PubMed  Google Scholar 

  95. Cipollone F, Mezzetti A, Fazia ML, Cuccurullo C, Iezzi A, Ucchino S et al (2005) Association between 5-lipoxygenase expression and plaque instability in humans. Arterioscler Thromb Vasc Biol 25(8):1665–1670

    Article  CAS  PubMed  Google Scholar 

  96. Tardif JC, L'Allier PL, Ibrahim R, Gregoire JC, Nozza A, Cossette M et al (2010) Treatment with 5-lipoxygenase inhibitor VIA-2291 (Atreleuton) in patients with recent acute coronary syndrome. Circ Cardiovasc Imaging 3(3):298–307

    Article  PubMed  Google Scholar 

  97. Hakonarson H, Thorvaldsson S, Helgadottir A, Gudbjartsson D, Zink F, Andresdottir M et al (2005) Effects of a 5-lipoxygenase-activating protein inhibitor on biomarkers associated with risk of myocardial infarction: a randomized trial. JAMA 293(18):2245–2256

    Article  CAS  PubMed  Google Scholar 

  98. Eid AA, Gorin Y, Fagg BM, Maalouf R, Barnes JL, Block K et al (2009) Mechanisms of podocyte injury in diabetes: role of cytochrome P450 and NADPH oxidases. Diabetes 58(5):1201–1211

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Rendic S, Di Carlo FJ (1997) Human cytochrome P450 enzymes: a status report summarizing their reactions, substrates, inducers, and inhibitors. Drug Metab Rev 29(1–2):413–580

    Article  CAS  PubMed  Google Scholar 

  100. Granville DJ, Tashakkor B, Takeuchi C, Gustafsson AB, Huang C, Sayen MR et al (2004) Reduction of ischemia and reperfusion-induced myocardial damage by cytochrome P450 inhibitors. Proc Natl Acad Sci U S A 101(5):1321–1326

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Hunter AL, Cruz RP, Cheyne BM, McManus BM, Granville DJ (2004) Cytochrome p450 enzymes and cardiovascular disease. Can J Physiol Pharmacol 82(12):1053–1060

    Article  CAS  PubMed  Google Scholar 

  102. Grobe AC, Wells SM, Benavidez E, Oishi P, Azakie A, Fineman JR et al (2006) Increased oxidative stress in lambs with increased pulmonary blood flow and pulmonary hypertension: role of NADPH oxidase and endothelial NO synthase. Am J Physiol Lung Cell Mol Physiol 290(6):L1069–L1077

    Article  CAS  PubMed  Google Scholar 

  103. Antoniades C, Shirodaria C, Leeson P, Antonopoulos A, Warrick N, Van-Assche T et al (2009) Association of plasma asymmetrical dimethylarginine (ADMA) with elevated vascular superoxide production and endothelial nitric oxide synthase uncoupling: implications for endothelial function in human atherosclerosis. Eur Heart J 30(9):1142–1150

    Article  CAS  PubMed  Google Scholar 

  104. Verhaar MC, Wever RM, Kastelein JJ, van Dam T, Koomans HA, Rabelink TJ (1998) 5-methyltetrahydrofolate, the active form of folic acid, restores endothelial function in familial hypercholesterolemia. Circulation 97(3):237–241

    Article  CAS  PubMed  Google Scholar 

  105. Brownlee M (2005) The pathobiology of diabetic complications: a unifying mechanism. Diabetes 54(6):1615–1625

    Article  CAS  PubMed  Google Scholar 

  106. Widlansky ME, Wang J, Shenouda SM, Hagen TM, Smith AR, Kizhakekuttu TJ et al (2010) Altered mitochondrial membrane potential, mass, and morphology in the mononuclear cells of humans with type 2 diabetes. Transl Res 156(1):15–25

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Crespo FL, Sobrado VR, Gomez L, Cervera AM, McCreath KJ (2010) Mitochondrial reactive oxygen species mediate cardiomyocyte formation from embryonic stem cells in high glucose. Stem Cells 28(7):1132–1142

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Handy DE, Loscalzo J (2012) Redox regulation of mitochondrial function. Antioxid Redox Signal 16(11):1323–1367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Zorov DB, Filburn CR, Klotz LO, Zweier JL, Sollott SJ (2000) Reactive oxygen species (ROS)-induced ROS release: a new phenomenon accompanying induction of the mitochondrial permeability transition in cardiac myocytes. J Exp Med 192(7):1001–1014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Zorov DB, Juhaszova M, Sollott SJ (2014) Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol Rev 94(3):909–950

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Nojiri H, Shimizu T, Funakoshi M, Yamaguchi O, Zhou H, Kawakami S et al (2006) Oxidative stress causes heart failure with impaired mitochondrial respiration. J Biol Chem 281(44):33789–33801

    Article  CAS  PubMed  Google Scholar 

  113. Li Y, Huang TT, Carlson EJ, Melov S, Ursell PC, Olson JL et al (1995) Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase. Nat Genet 11(4):376–381

    Article  CAS  PubMed  Google Scholar 

  114. Matsushima S, Ide T, Yamato M, Matsusaka H, Hattori F, Ikeuchi M et al (2006) Overexpression of mitochondrial peroxiredoxin-3 prevents left ventricular remodeling and failure after myocardial infarction in mice. Circulation 113(14):1779–1786

    Article  CAS  PubMed  Google Scholar 

  115. Ben-Hail D, Begas-Shvartz R, Shalev M, Shteinfer-Kuzmine A, Gruzman A, Reina S et al (2016) Novel compounds targeting the mitochondrial protein VDAC1 inhibit apoptosis and protect against mitochondrial dysfunction. J Biol Chem 291(48):24986–25003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Li X, Fang P, Li Y, Kuo YM, Andrews AJ, Nanayakkara G et al (2016) Mitochondrial reactive oxygen species mediate lysophosphatidylcholine-induced endothelial cell activation. Arterioscler Thromb Vasc Biol 36(6):1090–1100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Chacko BK, Reily C, Srivastava A, Johnson MS, Ye Y, Ulasova E et al (2010) Prevention of diabetic nephropathy in Ins2(+/)(−)(AkitaJ) mice by the mitochondria-targeted therapy MitoQ. Biochem J 432(1):9–19

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Karin Jandeleit-Dahm .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Jha, J.C., Bose, M., Jandeleit-Dahm, K. (2019). Modulation of Oxidative Stress in Cardiovascular Diseases. In: Chakraborti, S., Dhalla, N., Dikshit, M., Ganguly, N. (eds) Modulation of Oxidative Stress in Heart Disease. Springer, Singapore. https://doi.org/10.1007/978-981-13-8946-7_10

Download citation

Publish with us

Policies and ethics