Advertisement

Functional Implications of Reactive Oxygen Species (ROS) in Human Blood Vessels

  • Tomasz J. Guzik
  • Agata Schramm
  • Marta Czesnikiewicz-Guzik
Reference work entry

Abstract

Reactive oxygen species (ROS) play a significant role in the pathogenesis of human vascular disorders associated with endothelial dysfunction, such as atherosclerosis, hypertension, coronary artery disease, and diabetic vascular disease. Moreover, recent data show that ROS are also relevant in venous diseases such as venous insufficiency or varicose vein disease (Guzik et al. 2011).

In general, the functional role of ROS in human vasculature is consistent with the majority of findings in animal models and cell culture, with main differences being related to the complexity of the system. This complexity is related not only to the concomitant expression of numerous oxidases (including Nox5) in human vessels in vivo but primarily to complicated regulation by many coinciding factors. While this is the case for every translational approach, for studies of reactive oxygen species, the task becomes particularly difficult. Furthermore, vascular pathologies in humans are much more dynamic and progress through more complex stages than observed in animal models. In humans, the sources and functional importance of ROS appear to differ at various stages of atherosclerotic plaque development. However, a number of solid studies have been performed on relatively large populations of subjects, and there is clear evidence as to the functional role of ROS in human vasculature and their regulation, which will be briefly discussed here.

Similar to animal models, ROS are generated by all layers of the vascular wall, the endothelium, vascular smooth muscle cells (VSMCs) in the media, fibroblasts, and incoming inflammatory cells in the adventitia (Berry et al. 2000). In these compartments, ROS may have divergent sources and roles, although its effects on endothelial function and vascular nitric oxide bioavailability appear to be particularly important in relation to human vascular disease.

Keywords

Reactive Oxygen Species Nitric Oxide Reactive Oxygen Species Production Chronic Heart Failure NADPH Oxidase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Adams V et al (2005) Impact of regular physical activity on the NAD(P)H oxidase and angiotensin receptor system in patients with coronary artery disease. Circulation 111(5):555–562PubMedGoogle Scholar
  2. Alp NJ, Channon KM (2004) Regulation of endothelial nitric oxide synthase by tetrahydrobiopterin in vascular disease. Arterioscler Thromb Vasc Biol 24(3):413–420PubMedGoogle Scholar
  3. Anderson TJ et al (1995a) Close relation of endothelial function in the human coronary and peripheral circulations. JACC 26:1235–1241PubMedGoogle Scholar
  4. Anderson TJ et al (1995b) The effect of cholesterol-lowering and antioxidant therapy on endothelium-dependent coronary vasomotion. N Engl J Med 332(8):488–493PubMedGoogle Scholar
  5. Antoniades C et al (2006) 5-methyltetrahydrofolate rapidly improves endothelial function and decreases superoxide production in human vessels: effects on vascular tetrahydrobiopterin availability and endothelial nitric oxide synthase coupling. Circulation 114(11):1193–1201PubMedGoogle Scholar
  6. Antoniades C et al (2007) Altered plasma versus vascular biopterins in human atherosclerosis reveal relationships between endothelial nitric oxide synthase coupling, endothelial function, and inflammation. Circulation 116(24):2851–2859PubMedGoogle Scholar
  7. Antoniades C et al (2008) GCH1 haplotype determines vascular and plasma biopterin availability in coronary artery disease effects on vascular superoxide production and endothelial function. J Am Coll Cardiol 52(2):158–165PubMedCentralPubMedGoogle Scholar
  8. Antoniades C et al (2009) MTHFR 677 C > T Polymorphism reveals functional importance for 5-methyltetrahydrofolate, not homocysteine, in regulation of vascular redox state and endothelial function in human atherosclerosis. Circulation 119(18):2507–2515PubMedGoogle Scholar
  9. Antoniades C et al (2011a) Induction of vascular GTP-cyclohydrolase I and endogenous tetrahydrobiopterin synthesis protect against inflammation-induced endothelial dysfunction in human atherosclerosis. Circulation 124(17):1860–1870PubMedGoogle Scholar
  10. Antoniades C et al (2011b) Rapid, direct effects of statin treatment on arterial redox state and nitric oxide bioavailability in human atherosclerosis via tetrahydrobiopterin-mediated endothelial nitric oxide synthase coupling. Circulation 124(3):335–345PubMedGoogle Scholar
  11. Azhar S (2010) Peroxisome proliferator-activated receptors, metabolic syndrome and cardiovascular disease. Future Cardiol 6(5):657–691PubMedCentralPubMedGoogle Scholar
  12. Azumi H et al (2002) Superoxide generation in directional coronary atherectomy specimens of patients with angina pectoris: important role of NAD(P)H oxidase. Arterioscler Thromb Vasc Biol 22(11):1838–1844PubMedGoogle Scholar
  13. Baehner RL, Karnovsky ML (1968) Deficiency of reduced nicotinamide-adenine dinucleotide oxidase in chronic granulomatous disease. Science 162(3859):1277–1279PubMedGoogle Scholar
  14. Bao W et al (2007) Effects of p38 MAPK Inhibitor on angiotensin II-dependent hypertension, organ damage, and superoxide anion production. J Cardiovasc Pharmacol 49(6):362–368PubMedGoogle Scholar
  15. Bayraktutan U, Blayney L, Shah AM (2000) Molecular characterization and localization of the NAD(P)H oxidase components gp91-phox and p22-phox in endothelial cells. Arterioscler Thromb Vasc Biol 20(8):1903–1911PubMedGoogle Scholar
  16. Berry C et al (2000) Investigation into the sources of superoxide in human blood vessels: angiotensin II increases superoxide production in human internal mammary arteries. Circulation 101(18):2206–2212PubMedGoogle Scholar
  17. Betarbet R et al (2000) Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nat Neurosci 3(12):1301–1306PubMedGoogle Scholar
  18. Bjelakovic G et al (2007) Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA 297(8):842–857PubMedGoogle Scholar
  19. Bobryshev YV, Lord RS (1995) S-100 positive cells in human arterial intima and in atherosclerotic lesions. Cardiovasc Res 29(5):689–696PubMedGoogle Scholar
  20. Bonetti PO, Lerman LO, Lerman A (2003) Endothelial dysfunction: a marker of atherosclerotic risk. Arterioscler Thromb Vasc Biol 23(2):168–175PubMedGoogle Scholar
  21. Bowry VW et al (1995) Prevention of tocopherol-mediated peroxidation in ubiquinol-10-free human low density lipoprotein. J Biol Chem 270(11):5756–5763PubMedGoogle Scholar
  22. Brownlee M (1995) Advanced protein glycosylation in diabetes and aging. Annu Rev Med 46:223–234PubMedGoogle Scholar
  23. Brownlee M (2005) The pathobiology of diabetic complications: a unifying mechanism. Diabetes 54(6):1615–1625PubMedGoogle Scholar
  24. Bubolz AH et al (2012) Activation of endothelial TRPV4 channels mediates flow-induced dilation in human coronary arterioles: role of Ca2+ entry and mitochondrial ROS signaling. Am J Physiol Heart Circ Physiol 302(3):H634–H642PubMedCentralPubMedGoogle Scholar
  25. Cahilly C et al (2000) A variant of p22(phox), involved in generation of reactive oxygen species in the vessel wall, is associated with progression of coronary atherosclerosis. Circ Res 86(4):391–395PubMedGoogle Scholar
  26. Cai H, Harrison DG (2000) Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res 87(10):840–844PubMedGoogle Scholar
  27. Cai H et al (1999) NADH/NADPH oxidase p22 phox C242T polymorphism and coronary artery disease in the Australian population. Eur J Clin Invest 29(9):744–748PubMedGoogle Scholar
  28. Cao X et al (2012) Angiotensin II-dependent hypertension requires cyclooxygenase 1-derived prostaglandin E2 and EP1 receptor signaling in the subfornical organ of the brain. Hypertension 59(4):869–876PubMedCentralPubMedGoogle Scholar
  29. Cascino T et al (2011) Adventitia-derived hydrogen peroxide impairs relaxation of the rat carotid artery via smooth muscle cell p38 mitogen-activated protein kinase. Antioxid Redox Signal 15(6):1507–1515PubMedCentralPubMedGoogle Scholar
  30. Cathcart MK (2004) Regulation of superoxide anion production by NADPH oxidase in monocytes/macrophages: contributions to atherosclerosis. Arterioscler Thromb Vasc Biol 24(1):23–28PubMedGoogle Scholar
  31. Cosentino F et al (1997) High glucose increases nitric oxide synthase expression and superoxide anion generation in human aortic endothelial cells. Circulation 96(1):25–28PubMedGoogle Scholar
  32. De Keulenaer GW et al (1998) Oscillatory and steady laminar shear stress differentially affect human endothelial redox state: role of a superoxide-producing NADH oxidase. Circ Res 82(10):1094–1101PubMedGoogle Scholar
  33. Doehner W et al (2002) Effects of xanthine oxidase inhibition with allopurinol on endothelial function and peripheral blood flow in hyperuricemic patients with chronic heart failure: results from 2 placebo-controlled studies. Circulation 105(22):2619–2624PubMedGoogle Scholar
  34. Doughan AK, Harrison DG, Dikalov SI (2008) Molecular mechanisms of angiotensin II-mediated mitochondrial dysfunction: linking mitochondrial oxidative damage and vascular endothelial dysfunction. Circ Res 102(4):488–496PubMedGoogle Scholar
  35. Dowd P, Zheng ZB (1995) On the mechanism of the anticlotting action of vitamin E quinone. Proc Natl Acad Sci U S A 92(18):8171–8175PubMedCentralPubMedGoogle Scholar
  36. Drexler H et al (1992) Endothelial function in chronic congestive heart failure. Am J Cardiol 69(19):1596–1601PubMedGoogle Scholar
  37. Ennezat PV et al (2011) Imagine how many lives you save: angiotensin-converting enzyme inhibition for atherosclerotic vascular disease in the present era of risk reduction. Expert Opin Pharmacother 12(6):883–897PubMedGoogle Scholar
  38. Gardemann A et al (1999) The p22 phox A640G gene polymorphism but not the C242T gene variation is associated with coronary heart disease in younger individuals. Atherosclerosis 145(2):315–323PubMedGoogle Scholar
  39. Gongora MC et al (2008) Loss of extracellular superoxide dismutase leads to acute lung damage in the presence of ambient air: a potential mechanism underlying adult respiratory distress syndrome. Am J Pathol 173(4):915–926PubMedCentralPubMedGoogle Scholar
  40. Greenberg ER (2005) Vitamin E supplements: good in theory, but is the theory good? Ann Intern Med 142(1):75–76PubMedGoogle Scholar
  41. Gryglewski RJ, Palmer RM, Moncada S (1986) Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor. Nature 320(6061):454–456PubMedGoogle Scholar
  42. Gutierrez AD et al (2009) The response of gamma vitamin E to varying dosages of alpha vitamin E plus vitamin C. Metabolism 58(4):469–478PubMedCentralPubMedGoogle Scholar
  43. Guzik TJ, Harrison DG (2006) Vascular NADPH oxidases as drug targets for novel antioxidant strategies. Drug Discov Today 11(11–12):524–533PubMedGoogle Scholar
  44. Guzik TJ, Harrison DG (2007) Endothelial NF-kappaB as a mediator of kidney damage: the missing link between systemic vascular and renal disease? Circ Res 101(3):227–229PubMedGoogle Scholar
  45. Guzik TJ et al (2000a) Vascular superoxide production by NAD(P)H oxidase: association with endothelial dysfunction and clinical risk factors. Circ Res 86(9):E85–E90PubMedGoogle Scholar
  46. Guzik TJ et al (2000b) Functional effect of the C242T polymorphism in the NAD(P)H oxidase p22phox gene on vascular superoxide production in atherosclerosis. Circulation 102(15):1744–1747PubMedGoogle Scholar
  47. Guzik TJ et al (2002) Mechanisms of increased vascular superoxide production in human diabetes mellitus: role of NAD(P)H oxidase and endothelial nitric oxide synthase. Circulation 105(14):1656–1662PubMedGoogle Scholar
  48. Guzik TJ et al (2004) Systemic regulation of vascular NAD(P)H oxidase activity and nox isoform expression in human arteries and veins. Arterioscler Thromb Vasc Biol 24(9):1614–1620PubMedGoogle Scholar
  49. Guzik TJ et al (2006) Coronary artery superoxide production and nox isoform expression in human coronary artery disease. Arterioscler Thromb Vasc Biol 26(2):333–339PubMedGoogle Scholar
  50. Guzik TJ et al (2008) Calcium-dependent NOX5 nicotinamide adenine dinucleotide phosphate oxidase contributes to vascular oxidative stress in human coronary artery disease. J Am Coll Cardiol 52(22):1803–1809PubMedCentralPubMedGoogle Scholar
  51. Guzik B et al (2011) Mechanisms of increased vascular superoxide production in human varicose veins. Pol Arch Med Wewn 121(9):279–286PubMedGoogle Scholar
  52. Heitzer T et al (2001) Endothelial dysfunction, oxidative stress, and risk of cardiovascular events in patients with coronary artery disease. Circulation 104(22):2673–2678PubMedGoogle Scholar
  53. Higgins P et al (2012) Xanthine oxidase inhibition for the treatment of cardiovascular disease: a systematic review and meta-analysis. Cardiovasc Ther 30(4):217–226PubMedGoogle Scholar
  54. Huang HY, Appel LJ (2003) Supplementation of diets with alpha-tocopherol reduces serum concentrations of gamma- and delta-tocopherol in humans. J Nutr 133(10):3137–3140PubMedGoogle Scholar
  55. Huraux C et al (1999) Superoxide production, risk factors, and endothelium-dependent relaxations in human internal mammary arteries. Circulation 99(1):53–59PubMedGoogle Scholar
  56. Hwang J et al (2003) Pulsatile versus oscillatory shear stress regulates NADPH oxidase subunit expression. Implication for native LDL oxidation. Circ Res 93(12):1225–1232PubMedGoogle Scholar
  57. Inoue N et al (1998) Polymorphism of the NADH/NADPH oxidase p22 phox gene in patients with coronary artery disease. Circulation 97(2):135–137PubMedGoogle Scholar
  58. Jay DB et al (2008) Nox5 mediates PDGF-induced proliferation in human aortic smooth muscle cells. Free Radic Biol Med 45(3):329–335PubMedCentralPubMedGoogle Scholar
  59. Kaminski PM, Wolin MS (1994) Hypoxia increases superoxide anion production from bovine coronary microvessels, but not cardiac myocytes, via increased xanthine oxidase. Microcirculation 1(4):231–236PubMedGoogle Scholar
  60. Kim C, Kim JY, Kim JH (2008) Cytosolic phospholipase A(2), lipoxygenase metabolites, and reactive oxygen species. BMB Rep 41(8):555–559PubMedGoogle Scholar
  61. Krzysciak W, Kozka M (2011) Generation of reactive oxygen species by a sufficient, insufficient and varicose vein wall. Acta Biochim Pol 58(1):89–94PubMedGoogle Scholar
  62. Kubo SH et al (1991) Endothelium-dependent vasodilation is attenuated in patients with heart failure. Circulation 84(4):1589–1596PubMedGoogle Scholar
  63. Kume N, Cybulsky MI, Gimbrone MA Jr (1992) Lysophosphatidylcholine, a component of atherogenic lipoproteins, induces mononuclear leukocyte adhesion molecules in cultured human and rabbit arterial endothelial cells. J Clin Invest 90(3):1138–1144PubMedCentralPubMedGoogle Scholar
  64. Kuzkaya N et al (2003) Interactions of peroxynitrite, tetrahydrobiopterin, ascorbic acid, and thiols: implications for uncoupling endothelial nitric-oxide synthase. J Biol Chem 278(25):22546–22554PubMedGoogle Scholar
  65. Landmesser U et al (2002a) Vascular oxidative stress and endothelial dysfunction in patients with chronic heart failure: role of xanthine-oxidase and extracellular superoxide dismutase. Circulation 106(24):3073–3078PubMedGoogle Scholar
  66. Landmesser U et al (2002b) Role of p47(phox) in vascular oxidative stress and hypertension caused by angiotensin II. Hypertension 40(4):511–515PubMedGoogle Scholar
  67. Landmesser U et al (2003) Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension. J Clin Invest 111(8):1201–1209PubMedCentralPubMedGoogle Scholar
  68. Lassegue B et al (2001) Novel gp91(phox) homologues in vascular smooth muscle cells: nox1 mediates angiotensin II-induced superoxide formation and redox-sensitive signaling pathways. Circ Res 88(9):888–894PubMedGoogle Scholar
  69. Laufs U et al (1998) Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation 97(12):1129–1135PubMedGoogle Scholar
  70. Leyva F et al (1997) Serum uric acid as an index of impaired oxidative metabolism in chronic heart failure. Eur Heart J 18(5):858–865PubMedGoogle Scholar
  71. Loukogeorgakis SP et al (2010) Role of NADPH oxidase in endothelial ischemia/reperfusion injury in humans. Circulation 121(21):2310–2316PubMedGoogle Scholar
  72. Lu X et al (2011) Reactive oxygen species cause endothelial dysfunction in chronic flow overload. J Appl Physiol 110(2):520–527PubMedCentralPubMedGoogle Scholar
  73. McLenachan JM et al (1990) Early evidence of endothelial vasodilator dysfunction at coronary branch points. Circulation 82(4):1169–1173PubMedGoogle Scholar
  74. Miguel-Carrasco, J.L., et al., Captopril reduces cardiac inflammatory markers in spontaneously hypertensive rats by inactivation of NF-kB. J Inflamm (Lond), 2010. 7: p. 21.Google Scholar
  75. Miller ER 3rd et al (2005) Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 142(1):37–46PubMedGoogle Scholar
  76. Morawietz H et al (2006a) Endothelial protection, AT1 blockade and cholesterol-dependent oxidative stress: the EPAS trial. Circulation 114(1 Suppl):I296–I301PubMedGoogle Scholar
  77. Morawietz H et al (2006b) Increased cardiac endothelial nitric oxide synthase expression in patients taking angiotensin-converting enzyme inhibitor therapy. Eur J Clin Invest 36(10):705–712PubMedGoogle Scholar
  78. Mueller CF et al (2005) ATVB in focus: redox mechanisms in blood vessels. Arterioscler Thromb Vasc Biol 25(2):274–278PubMedGoogle Scholar
  79. Neunteufl T et al (1997) Systemic endothelial dysfunction is related to the extent and severity of coronary artery disease. Atherosclerosis 129(1):111–118PubMedGoogle Scholar
  80. Nielsen VG et al (1997) Xanthine oxidase mediates myocardial injury after hepatoenteric ischemia-reperfusion. Crit Care Med 25(6):1044–1050PubMedGoogle Scholar
  81. Nissen SE et al (2004) Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure: the CAMELOT study: a randomized controlled trial. JAMA 292(18):2217–2225PubMedGoogle Scholar
  82. Pacher P, Beckman JS, Liaudet L (2007) Nitric oxide and peroxynitrite in health and disease. Physiol Rev 87(1):315–424PubMedCentralPubMedGoogle Scholar
  83. Paravicini TM et al (2012) Activation of vascular p38MAPK by mechanical stretch is independent of c-Src and NADPH oxidase: influence of hypertension and angiotensin II. J Am Soc Hypertens 6(3):169–178PubMedGoogle Scholar
  84. Polikandriotis JA et al (2005) Peroxisome proliferator-activated receptor gamma ligands stimulate endothelial nitric oxide production through distinct peroxisome proliferator-activated receptor gamma-dependent mechanisms. Arterioscler Thromb Vasc Biol 25(9):1810–1816PubMedGoogle Scholar
  85. Rajagopalan S et al (1996) Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro. Implications for atherosclerotic plaque stability. J Clin Invest 98(11):2572–2579PubMedCentralPubMedGoogle Scholar
  86. Ray R, Shah AM (2005) NADPH oxidase and endothelial cell function. Clin Sci (Lond) 109(3):217–226Google Scholar
  87. Rey FE et al (2002) Perivascular superoxide anion contributes to impairment of endothelium-dependent relaxation: role of gp91(phox). Circulation 106(19):2497–2502PubMedGoogle Scholar
  88. Rueckschloss U et al (2002) Dose-dependent regulation of NAD(P)H oxidase expression by angiotensin II in human endothelial cells: protective effect of angiotensin II type 1 receptor blockade in patients with coronary artery disease. Arterioscler Thromb Vasc Biol 22(11):1845–1851PubMedGoogle Scholar
  89. Saavedra WF et al (2002) Imbalance between xanthine oxidase and nitric oxide synthase signaling pathways underlies mechanoenergetic uncoupling in the failing heart. Circ Res 90(3):297–304PubMedGoogle Scholar
  90. Sauer, H., A.M. Shah, and F.R.M. Laurindo, Studies on cardiovascular disorders. Oxidative stress in applied basic research and clinical practice 2010, New York: Humana Press. xvii, 587 p.Google Scholar
  91. Schramm A et al (2012) Targeting NADPH oxidases in vascular pharmacology. Vascul Pharmacol 56(5–6):216–231PubMedCentralPubMedGoogle Scholar
  92. Sherer TB et al (2007) Mechanism of toxicity of pesticides acting at complex I: relevance to environmental etiologies of Parkinson’s disease. J Neurochem 100(6):1469–1479PubMedGoogle Scholar
  93. Shirodaria C et al (2007) Global improvement of vascular function and redox state with low-dose folic acid: implications for folate therapy in patients with coronary artery disease. Circulation 115(17):2262–2270PubMedGoogle Scholar
  94. Sorescu D et al (2002) Superoxide production and expression of nox family proteins in human atherosclerosis. Circulation 105(12):1429–1435PubMedGoogle Scholar
  95. Sorrentino SA et al (2007) Oxidant stress impairs in vivo reendothelialization capacity of endothelial progenitor cells from patients with type 2 diabetes mellitus: restoration by the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone. Circulation 116(2):163–173PubMedGoogle Scholar
  96. Spiekermann S et al (2003) Electron spin resonance characterization of vascular xanthine and NAD(P)H oxidase activity in patients with coronary artery disease: relation to endothelium-dependent vasodilation. Circulation 107(10):1383–1389PubMedGoogle Scholar
  97. Stanic B et al (2012) Increased epidermal growth factor-like ligands are associated with elevated vascular nicotinamide adenine dinucleotide phosphate oxidase in a primate model of atherosclerosis. Arterioscler Thromb Vasc Biol 32(10):2452–2460PubMedCentralPubMedGoogle Scholar
  98. Stephens NG et al (1996) Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet 347(9004):781–786PubMedGoogle Scholar
  99. Stirpe F, Della Corte E (1969) The regulation of rat liver xanthine oxidase. Conversion in vitro of the enzyme activity from dehydrogenase (type D) to oxidase (type O). J Biol Chem 244(14):3855–3863PubMedGoogle Scholar
  100. Suh YA et al (1999) Cell transformation by the superoxide-generating oxidase Mox1. Nature 401(6748):79–82PubMedGoogle Scholar
  101. Szocs K et al (2002) Upregulation of Nox-based NAD(P)H oxidases in restenosis after carotid injury. Arterioscler Thromb Vasc Biol 22(1):21–27PubMedGoogle Scholar
  102. Tabet F et al (2008) Redox-sensitive signaling by angiotensin II involves oxidative inactivation and blunted phosphorylation of protein tyrosine phosphatase SHP-2 in vascular smooth muscle cells from SHR. Circ Res 103(2):149–158PubMedCentralPubMedGoogle Scholar
  103. Takimoto E, Kass DA (2007) Role of oxidative stress in cardiac hypertrophy and remodeling. Hypertension 49(2):241–248PubMedGoogle Scholar
  104. Tanner CM et al (2011) Rotenone, paraquat, and Parkinson's disease. Environ Health Perspect 119(6):866–872PubMedCentralPubMedGoogle Scholar
  105. Touyz RM et al (2002) Expression of a functionally active gp91phox-containing neutrophil-type NAD(P)H oxidase in smooth muscle cells from human resistance arteries: regulation by angiotensin II. Circ Res 90(11):1205–1213PubMedGoogle Scholar
  106. Ungvari Z et al (2003) Increased superoxide production in coronary arteries in hyperhomocysteinemia: role of tumor necrosis factor-alpha, NAD(P)H oxidase, and inducible nitric oxide synthase. Arterioscler Thromb Vasc Biol 23(3):418–424PubMedGoogle Scholar
  107. Ushio-Fukai M et al (1999) Reactive oxygen species mediate the activation of Akt/protein kinase B by angiotensin II in vascular smooth muscle cells. J Biol Chem 274(32):22699–22704PubMedGoogle Scholar
  108. Ushio-Fukai M et al (2001) Epidermal growth factor receptor transactivation by angiotensin II requires reactive oxygen species in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 21(4):489–495PubMedGoogle Scholar
  109. Van Haaften RI et al (2001) Inhibition of human glutathione S-transferase P1-1 by tocopherols and alpha-tocopherol derivatives. Biochim Biophys Acta 1548(1):23–28PubMedGoogle Scholar
  110. Vasquez-Vivar J, Kalyanaraman B, Martasek P (2003) The role of tetrahydrobiopterin in superoxide generation from eNOS: enzymology and physiological implications. Free Radic Res 37(2):121–127PubMedGoogle Scholar
  111. Vecchione C et al (2005) Protection from angiotensin II-mediated vasculotoxic and hypertensive response in mice lacking PI3Kgamma. J Exp Med 201(8):1217–1228PubMedCentralPubMedGoogle Scholar
  112. Violi F et al (2013) Reduced atherosclerotic burden in subjects with genetically determined low oxidative stress. Arterioscler Thromb Vasc Biol 33(2):406–412PubMedGoogle Scholar
  113. Wagner AH et al (2000) Improvement of nitric oxide-dependent vasodilatation by HMG-CoA reductase inhibitors through attenuation of endothelial superoxide anion formation. Arterioscler Thromb Vasc Biol 20(1):61–69PubMedGoogle Scholar
  114. Wali MA et al (2002) Superoxide radical concentration and superoxide dismutase (SOD) enzyme activity in varicose veins. Ann Thorac Cardiovasc Surg 8(5):286–290PubMedGoogle Scholar
  115. Wassmann S et al (2002) Cellular antioxidant effects of atorvastatin in vitro and in vivo. Arterioscler Thromb Vasc Biol 22(2):300–305PubMedGoogle Scholar
  116. West NEJ et al (2001) Enhanced superoxide production in experimental venous bypass graft intimal hyperplasia: role of NAD(P)H oxidase. Atheroscl Thromb Vasc Biol 21:189–194Google Scholar
  117. Wilcox JN et al (1997) Expression of multiple isoforms of nitric oxide synthase in normal and atherosclerotic vessels. Arterioscler Thromb Vasc Biol 17(11):2479–2488PubMedGoogle Scholar
  118. Yamada Y et al (2002) Prediction of the risk of myocardial infarction from polymorphisms in candidate genes. N Engl J Med 347(24):1916–1923PubMedGoogle Scholar
  119. Zafari AM et al (1998) Role of NADH/NADPH oxidase-derived H2O2 in angiotensin II-induced vascular hypertrophy. Hypertension 32(3):488–495PubMedGoogle Scholar
  120. Zernecke A, Shagdarsuren E, Weber C (2008) Chemokines in atherosclerosis: an update. Arterioscler Thromb Vasc Biol 28(11):1897–1908PubMedGoogle Scholar
  121. Zima AV, Blatter LA (2006) Redox regulation of cardiac calcium channels and transporters. Cardiovasc Res 71(2):310–321PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Tomasz J. Guzik
    • 1
  • Agata Schramm
    • 1
  • Marta Czesnikiewicz-Guzik
    • 1
  1. 1.Translational Medicine Laboratory, Department of Internal and Agricultural MedicineJagiellonian University School of MedicineCracowPoland

Personalised recommendations