Vascular oxidative stress, nitric oxide and atherosclerosis

Atherosclerosis

Volumn 237, Issue 1, 2014, Pages 208-219

  Li, Huige ^a   Horke, Sven ^a   Förstermann, Ulrich ^a  

^a UNIVERSITY MEDICAL CENTER MAINZ   (Germany)

Author keywords

Atherosclerosis; Nitric oxide; Oxidative stress; Reactive oxygen species

Indexed keywords

ANTIOXIDANT; ARYLDIALKYLPHOSPHATASE; CATALASE; ENDOTHELIAL NITRIC OXIDE SYNTHASE; GLUTATHIONE PEROXIDASE; INDUCIBLE NITRIC OXIDE SYNTHASE; NEURONAL NITRIC OXIDE SYNTHASE; NITRIC OXIDE; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE; SUPEROXIDE DISMUTASE; XANTHINE OXIDASE; SUPEROXIDE;

ATHEROGENESIS; ATHEROSCLEROSIS; BONE MARROW CELL; CARDIOVASCULAR RISK; GENETIC POLYMORPHISM; HUMAN; MITOCHONDRION; NONHUMAN; OXIDATIVE STRESS; REVIEW; ANIMAL; CARDIOVASCULAR SYSTEM; CHEMISTRY; METABOLISM; MOUSE; PATHOLOGY; TRANSGENIC MOUSE;

ANIMALS; ANTIOXIDANTS; ARYLDIALKYLPHOSPHATASE; ATHEROSCLEROSIS; CARDIOVASCULAR SYSTEM; CATALASE; GLUTATHIONE PEROXIDASE; HUMANS; MICE; MICE, TRANSGENIC; MITOCHONDRIA; NADPH OXIDASE; NITRIC OXIDE; NITRIC OXIDE SYNTHASE TYPE I; NITRIC OXIDE SYNTHASE TYPE III; OXIDATIVE STRESS; REACTIVE OXYGEN SPECIES; SUPEROXIDE DISMUTASE; SUPEROXIDES; XANTHINE OXIDASE;

EID: 84907766487     PISSN: 00219150     EISSN: 18791484     Source Type: Journal    
DOI: 10.1016/j.atherosclerosis.2014.09.001     Document Type: Review

References (171)

1. Zhang D.X., Gutterman D.D. Mitochondrial reactive oxygen species-mediated signaling in endothelial cells. Am J Physiol Heart Circ Physiol 2007, 292:H2023-2031.
2. Stocker R., Keaney J.F. Role of oxidative modifications in atherosclerosis. Physiol Rev 2004, 84:1381-1478.
3. Harrison D., Griendling K.K., Landmesser U., Hornig B., Drexler H. Role of oxidative stress in atherosclerosis. Am J Cardiol 2003, 91:7A-11A.
4. Forstermann U. Oxidative stress in vascular disease: causes, defense mechanisms and potential therapies. Nat Clin Pract Cardiovasc Med 2008, 5:338-349.
5. Li H., Forstermann U. Uncoupling of endothelial NO synthase in atherosclerosis and vascular disease. Curr Opin Pharmacol 2013, 13:161-167.
6. Borradaile N.M., Han X., Harp J.D., Gale S.E., Ory D.S., Schaffer J.E. Disruption of endoplasmic reticulum structure and integrity in lipotoxic cell death. JLipid Res 2006, 47:2726-2737.
7. Maxfield F.R., Tabas I. Role of cholesterol and lipid organization in disease. Nature 2005, 438:612-621.
8. Zhou J., Lhotak S., Hilditch B.A., Austin R.C. Activation of the unfolded protein response occurs at all stages of atherosclerotic lesion development in apolipoprotein E-deficient mice. Circulation 2005, 111:1814-1821.
9. Gargalovic P.S., Gharavi N.M., Clark M.J., Pagnon J., Yang W.P., He A., et al. The unfolded protein response is an important regulator of inflammatory genes in endothelial cells. Arterioscler Thromb Vasc Biol 2006, 26:2490-2496.
10. Galan M., Kassan M., Kadowitz P.J., Trebak M., Belmadani S., Matrougui K. Mechanism of endoplasmic reticulum stress-induced vascular endothelial dysfunction. Biochim Biophys Acta 2014, 1843:1063-1075.
11. Gorlach A., Klappa P., Kietzmann T. The endoplasmic reticulum: folding, calcium homeostasis, signaling, and redox control. Antioxid Redox Signal 2006, 8:1391-1418.
12. Tu B.P., Weissman J.S. Oxidative protein folding in eukaryotes: mechanisms and consequences. JCell Biol 2004, 164:341-346.
13. Devries-Seimon T., Li Y., Yao P.M., Stone E., Wang Y., Davis R.J., et al. Cholesterol-induced macrophage apoptosis requires ER stress pathways and engagement of the type A scavenger receptor. JCell Biol 2005, 171:61-73.
14. Feng B., Yao P.M., Li Y., Devlin C.M., Zhang D., Harding H.P., et al. The endoplasmic reticulum is the site of cholesterol-induced cytotoxicity in macrophages. Nat Cell Biol 2003, 5:781-792.
15. McCullough K.D., Martindale J.L., Klotz L.O., Aw T.Y., Holbrook N.J. Gadd153 sensitizes cells to endoplasmic reticulum stress by down-regulating Bcl2 and perturbing the cellular redox state. Mol Cell Biol 2001, 21:1249-1259.
16. Sovolyova N., Healy S., Samali A., Logue S.E. Stressed to death - mechanisms of ER stress-induced cell death. Biol Chem 2014, 395:1-13.
17. Gorman A.M., Healy S.J., Jager R., Samali A. Stress management at the ER: regulators of ER stress-induced apoptosis. Pharmacol Ther 2012, 134:306-316.
18. Zhou A.X., Tabas I. The UPR in atherosclerosis. Semin Immunopathol 2013, 35:321-332.
19. Ozcan L., Tabas I. Role of endoplasmic reticulum stress in metabolic disease and other disorders. Annu Rev Med 2012, 63:317-328.
20. Ozcan U., Yilmaz E., Ozcan L., Furuhashi M., Vaillancourt E., Smith R.O., et al. Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science 2006, 313:1137-1140.
21. Thorp E., Tabas I. Mechanisms and consequences of efferocytosis in advanced atherosclerosis. JLeukoc Biol 2009, 86:1089-1095.
22. Tsukano H., Gotoh T., Endo M., Miyata K., Tazume H., Kadomatsu T., et al. The endoplasmic reticulum stress-C/EBP homologous protein pathway-mediated apoptosis in macrophages contributes to the instability of atherosclerotic plaques. Arterioscler Thromb Vasc Biol 2010, 30:1925-1932.
23. Thorp E., Li G., Seimon T.A., Kuriakose G., Ron D., Tabas I. Reduced apoptosis and plaque necrosis in advanced atherosclerotic lesions of Apoe-/- and Ldlr-/- mice lacking CHOP. Cell Metab 2009, 9:474-481.
24. Breton-Romero R., Gonzalez de Orduna C., Romero N., Sanchez-Gomez F.J., de Alvaro C., Porras A., et al. Critical role of hydrogen peroxide signaling in the sequential activation of p38 MAPK and eNOS in laminar shear stress. Free Radic Biol Med 2012, 52:1093-1100.
25. Park J.G., Yoo J.Y., Jeong S.J., Choi J.H., Lee M.R., Lee M.N., et al. Peroxiredoxin 2 deficiency exacerbates atherosclerosis in apolipoprotein E-deficient mice. Circ Res 2011, 109:739-749.
26. Aono J., Suzuki J., Iwai M., Horiuchi M., Nagai T., Nishimura K., et al. Deletion of the angiotensin II type 1a receptor prevents atherosclerotic plaque rupture in apolipoprotein E-/- mice. Arterioscler Thromb Vasc Biol 2012, 32:1453-1459.
27. Han C., Liu J., Liu X., Li M. Angiotensin II induces C-reactive protein expression through ERK1/2 and JNK signaling in human aortic endothelial cells. Atherosclerosis 2010, 212:206-212.
28. Su J., Zhang T., Tyson J., Li L. The interleukin-1 receptor-associated kinase M selectively inhibits the alternative, instead of the classical NFkappaB pathway. JInnate Immun 2009, 1:164-174.
29. Landmesser U., Spiekermann S., Preuss C., Sorrentino S., Fischer D., Manes C., et al. Angiotensin II induces endothelial xanthine oxidase activation: role for endothelial dysfunction in patients with coronary disease. Arterioscler Thromb Vasc Biol 2007, 27:943-948.
30. Drummond G.R., Selemidis S., Griendling K.K., Sobey C.G. Combating oxidative stress in vascular disease: NADPH oxidases as therapeutic targets. Nat Rev Drug Discov 2011, 10:453-471.
31. Bedard K., Krause K.H. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 2007, 87:245-313.
32. Brandes R.P., Kreuzer J. Vascular NADPH oxidases: molecular mechanisms of activation. Cardiovasc Res 2005, 65:16-27.
33. Lassegue B., Sorescu D., Szocs K., Yin Q., Akers M., Zhang Y., et al. Novel gp91(phox) homologues in vascular smooth muscle cells: nox1 mediates angiotensin II-induced superoxide formation and redox-sensitive signaling pathways. Circ Res 2001, 88:888-894.
34. Ellmark S.H., Dusting G.J., Fui M.N., Guzzo-Pernell N., Drummond G.R. The contribution of Nox4 to NADPH oxidase activity in mouse vascular smooth muscle. Cardiovasc Res 2005, 65:495-504.
35. Gorlach A., Brandes R.P., Nguyen K., Amidi M., Dehghani F., Busse R. Agp91phox containing NADPH oxidase selectively expressed in endothelial cells is a major source of oxygen radical generation in the arterial wall. Circ Res 2000, 87:26-32.
36. Ago T., Kitazono T., Ooboshi H., Iyama T., Han Y.H., Takada J., et al. Nox4 as the major catalytic component of an endothelial NAD(P)H oxidase. Circulation 2004, 109:227-233.
37. Xu H., Goettsch C., Xia N., Horke S., Morawietz H., Forstermann U., et al. Differential roles of PKCalpha and PKCepsilon in controlling the gene expression of Nox4 in human endothelial cells. Free Radic Biol Med 2008, 44:1656-1667.
38. Guzik T.J., Sadowski J., Guzik B., Jopek A., Kapelak B., Przybylowski P., et al. Coronary artery superoxide production and nox isoform expression in human coronary artery disease. Arterioscler Thromb Vasc Biol 2006, 26:333-339.
39. Judkins C.P., Diep H., Broughton B.R., Mast A.E., Hooker E.U., Miller A.A., et al. Direct evidence of a role for Nox2 in superoxide production, reduced nitric oxide bioavailability, and early atherosclerotic plaque formation in ApoE-/- mice. Am J Physiol Heart Circ Physiol 2010, 298:H24-32.
40. Kirk E.A., Dinauer M.C., Rosen H., Chait A., Heinecke J.W., LeBoeuf R.C. Impaired superoxide production due to a deficiency in phagocyte NADPH oxidase fails to inhibit atherosclerosis in mice. Arterioscler Thromb Vasc Biol 2000, 20:1529-1535.
41. Hsich E., Segal B.H., Pagano P.J., Rey F.E., Paigen B., Deleonardis J., et al. Vascular effects following homozygous disruption of p47(phox): an essential component of NADPH oxidase. Circulation 2000, 101:1234-1236.
42. Barry-Lane P.A., Patterson C., van der Merwe M., Hu Z., Holland S.M., Yeh E.T., et al. p47phox is required for atherosclerotic lesion progression in ApoE(-/-) mice. JClin Invest 2001, 108:1513-1522.
43. Douglas G., Bendall J.K., Crabtree M.J., Tatham A.L., Carter E.E., Hale A.B., et al. Endothelial-specific Nox2 overexpression increases vascular superoxide and macrophage recruitment in ApoE(-)/(-) mice. Cardiovasc Res 2012, 94:20-29.
44. Sorescu D., Weiss D., Lassegue B., Clempus R.E., Szocs K., Sorescu G.P., et al. Superoxide production and expression of nox family proteins in human atherosclerosis. Circulation 2002, 105:1429-1435.
45. Haendeler J., Eckers A., Lukosz M., Unfried K., Altschmied J. Endothelial NADPH oxidase 2: when does it matter in atherosclerosis?. Cardiovasc Res 2012, 94:1-2.
46. White C.R., Darley-Usmar V., Berrington W.R., McAdams M., Gore J.Z., Thompson J.A., et al. Circulating plasma xanthine oxidase contributes to vascular dysfunction in hypercholesterolemic rabbits. Proc Natl Acad Sci U S A 1996, 93:8745-8749.
47. Ohara Y., Peterson T.E., Harrison D.G. Hypercholesterolemia increases endothelial superoxide anion production. JClin Invest 1993, 91:2546-2551.
48. Patetsios P., Song M., Shutze W.P., Pappas C., Rodino W., Ramirez J.A., et al. Identification of uric acid and xanthine oxidase in atherosclerotic plaque. Am J Cardiol 2001, 88:188-191. A186.
49. Guthikonda S., Sinkey C., Barenz T., Haynes W.G. Xanthine oxidase inhibition reverses endothelial dysfunction in heavy smokers. Circulation 2003, 107:416-421.
50. Schroder K., Vecchione C., Jung O., Schreiber J.G., Shiri-Sverdlov R., van Gorp P.J., et al. Xanthine oxidase inhibitor tungsten prevents the development of atherosclerosis in ApoE knockout mice fed a Western-type diet. Free Radic Biol Med 2006, 41:1353-1360.
51. Leopold J.A., Loscalzo J. Oxidative risk for atherothrombotic cardiovascular disease. Free Radic Biol Med 2009, 47:1673-1706.
52. Sugamura K., Keaney J.F. Reactive oxygen species in cardiovascular disease. Free Radic Biol Med 2011, 51:978-992.
53. Li Y., Huang T.T., Carlson E.J., Melov S., Ursell P.C., Olson J.L., et al. Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase. Nat Genet 1995, 11:376-381.
54. Nojiri H., Shimizu T., Funakoshi M., Yamaguchi O., Zhou H., Kawakami S., et al. Oxidative stress causes heart failure with impaired mitochondrial respiration. JBiol Chem 2006, 281:33789-33801.
55. Chouchani E.T., Methner C., Nadtochiy S.M., Logan A., Pell V.R., Ding S., et al. Cardioprotection by S-nitrosation of a cysteine switch on mitochondrial complex I. Nat Med 2013, 19:753-759.
56. Mercer J.R., Yu E., Figg N., Cheng K.K., Prime T.A., Griffin J.L., et al. The mitochondria-targeted antioxidant MitoQ decreases features of the metabolic syndrome in ATM+/-/ApoE-/- mice. Free Radic Biol Med 2012, 52:841-849.
57. Wang J., Yi Y., Li B., Wang Z., Sun H., Zhang P., et al. CYFRA21-1 can predict the sensitivity to chemoradiotherapy of non-small-cell lung carcinoma. Biomarkers 2010, 15:594-601.
58. Jin H., Kanthasamy A., Ghosh A., Anantharam V., Kalyanaraman B., Kanthasamy A.G. Mitochondria-targeted antioxidants for treatment of Parkinson's disease: preclinical and clinical outcomes. Biochim Biophys Acta 2014, 1842:1282-1294.
59. Yu E., Calvert P.A., Mercer J.R., Harrison J., Baker L., Figg N.L., et al. Mitochondrial DNA damage can promote atherosclerosis independently of reactive oxygen species through effects on smooth muscle cells and monocytes and correlates with higher-risk plaques in humans. Circulation 2013, 128:702-712.
60. Li H., Forstermann U. Nitric oxide in the pathogenesis of vascular disease. JPathol 2000, 190:244-254.
61. Li H., Forstermann U. Prevention of atherosclerosis by interference with the vascular nitric oxide system. Curr Pharm Des 2009, 15:3133-3145.
62. Forstermann U., Sessa W.C. Nitric oxide synthases: regulation and function. Eur Heart J 2012, 33. 829-837, 837a-837d.
63. Li H., Horke S., Forstermann U. Oxidative stress in vascular disease and its pharmacological prevention. Trends Pharmacol Sci 2013, 34:313-319.
64. Forstermann U., Munzel T. Endothelial nitric oxide synthase in vascular disease: from marvel to menace. Circulation 2006, 113:1708-1714.
65. Alp N.J., McAteer M.A., Khoo J., Choudhury R.P., Channon K.M. Increased endothelial tetrahydrobiopterin synthesis by targeted transgenic GTP-cyclohydrolase I overexpression reduces endothelial dysfunction and atherosclerosis in ApoE-knockout mice. Arterioscler Thromb Vasc Biol 2004, 24:445-450.
66. Wohlfart P., Xu H., Endlich A., Habermeier A., Closs E.I., Hubschle T., et al. Antiatherosclerotic effects of small-molecular-weight compounds enhancing endothelial nitric-oxide synthase (eNOS) expression and preventing eNOS uncoupling. JPharmacol Exp Ther 2008, 325:370-379.
67. Xia N., Daiber A., Habermeier A., Closs E.I., Thum T., Spanier G., et al. Resveratrol reverses endothelial nitric-oxide synthase uncoupling in apolipoprotein E knockout mice. JPharmacol Exp Ther 2010, 335:149-154.
68. Stroes E., Kastelein J., Cosentino F., Erkelens W., Wever R., Koomans H., et al. Tetrahydrobiopterin restores endothelial function in hypercholesterolemia. JClin Invest 1997, 99:41-46.
69. Heitzer T., Krohn K., Albers S., Meinertz T. Tetrahydrobiopterin improves endothelium-dependent vasodilation by increasing nitric oxide activity in patients with type II diabetes mellitus. Diabetologia 2000, 43:1435-1438.
70. Ueda S., Matsuoka H., Miyazaki H., Usui M., Okuda S., Imaizumi T. Tetrahydrobiopterin restores endothelial function in long-term smokers. JAm Coll Cardiol 2000, 35:71-75.
71. 2 production in mouse cerebral arteries. Cardiovasc Res 2007, 73:73-81.
72. Drouin A., Thorin E. Flow-induced dilation is mediated by Akt-dependent activation of endothelial nitric oxide synthase-derived hydrogen peroxide in mouse cerebral arteries. Stroke 2009, 40:1827-1833.
73. Yokoyama M., Hirata K. Endothelial nitric oxide synthase uncoupling: is it a physiological mechanism of endothelium-dependent relaxation in cerebral artery?. Cardiovasc Res 2007, 73:8-9.
74. Fukai T., Ushio-Fukai M. Superoxide dismutases: role in redox signaling, vascular function, and diseases. Antioxid Redox Signal 2011, 15:1583-1606.
75. Tribble D.L., Gong E.L., Leeuwenburgh C., Heinecke J.W., Carlson E.L., Verstuyft J.G., et al. Fatty streak formation in fat-fed mice expressing human copper-zinc superoxide dismutase. Arterioscler Thromb Vasc Biol 1997, 17:1734-1740.
76. Nelson S.K., Bose S.K., McCord J.M. The toxicity of high-dose superoxide dismutase suggests that superoxide can both initiate and terminate lipid peroxidation in the reperfused heart. Free Radic Biol Med 1994, 16:195-200.
77. Yang H., Roberts L.J., Shi M.J., Zhou L.C., Ballard B.R., Richardson A., et al. Retardation of atherosclerosis by overexpression of catalase or both Cu/Zn-superoxide dismutase and catalase in mice lacking apolipoprotein E. Circ Res 2004, 95:1075-1081.
78. Ballinger S.W., Patterson C., Knight-Lozano C.A., Burow D.L., Conklin C.A., Hu Z., et al. Mitochondrial integrity and function in atherogenesis. Circulation 2002, 106:544-549.
79. Sentman M.L., Brannstrom T., Westerlund S., Laukkanen M.O., Yla-Herttuala S., Basu S., et al. Extracellular superoxide dismutase deficiency and atherosclerosis in mice. Arterioscler Thromb Vasc Biol 2001, 21:1477-1482.
80. 2. Hypertension 2005, 46:732-737.
81. Yang H., Zhou L., Wang Z., Roberts L.J., Lin X., Zhao Y., et al. Overexpression of antioxidant enzymes in ApoE-deficient mice suppresses benzo(a)pyrene-accelerated atherosclerosis. Atherosclerosis 2009, 207:51-58.
82. Asmis R., Begley J.G. Oxidized LDL promotes peroxide-mediated mitochondrial dysfunction and cell death in human macrophages: a caspase-3-independent pathway. Circ Res 2003, 92:e20-29.
83. Tribble D.L., Barcellos-Hoff M.H., Chu B.M., Gong E.L. Ionizing radiation accelerates aortic lesion formation in fat-fed mice via SOD-inhibitable processes. Arterioscler Thromb Vasc Biol 1999, 19:1387-1392.
84. Lubos E., Loscalzo J., Handy D.E. Glutathione peroxidase-1 in health and disease: from molecular mechanisms to therapeutic opportunities. Antioxid Redox Signal 2011, 15:1957-1997.
85. Blankenberg S., Rupprecht H.J., Bickel C., Torzewski M., Hafner G., Tiret L., et al. Glutathione peroxidase 1 activity and cardiovascular events in patients with coronary artery disease. NEngl J Med 2003, 349:1605-1613.
86. Cheng F., Torzewski M., Degreif A., Rossmann H., Canisius A., Lackner K.J. Impact of glutathione peroxidase-1 deficiency on macrophage foam cell formation and proliferation: implications for atherogenesis. PLoS One 2013, 8:e72063.
87. de Haan J.B., Witting P.K., Stefanovic N., Pete J., Daskalakis M., Kola I., et al. Lack of the antioxidant glutathione peroxidase-1 does not increase atherosclerosis in C57BL/J6 mice fed a high-fat diet. JLipid Res 2006, 47:1157-1167.
88. Torzewski M., Ochsenhirt V., Kleschyov A.L., Oelze M., Daiber A., Li H., et al. Deficiency of glutathione peroxidase-1 accelerates the progression of atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 2007, 27:850-857.
89. Lewis P., Stefanovic N., Pete J., Calkin A.C., Giunti S., Thallas-Bonke V., et al. Lack of the antioxidant enzyme glutathione peroxidase-1 accelerates atherosclerosis in diabetic apolipoprotein E-deficient mice. Circulation 2007, 115:2178-2187.
90. Chew P., Yuen D.Y., Koh P., Stefanovic N., Febbraio M.A., Kola I., et al. Site-specific antiatherogenic effect of the antioxidant ebselen in the diabetic apolipoprotein E-deficient mouse. Arterioscler Thromb Vasc Biol 2009, 29:823-830.
91. Imai H., Nakagawa Y. Biological significance of phospholipid hydroperoxide glutathione peroxidase (PHGPx, GPx4) in mammalian cells. Free Radic Biol Med 2003, 34:145-169.
92. Guo Z., Ran Q., Roberts L.J., Zhou L., Richardson A., Sharan C., et al. Suppression of atherogenesis by overexpression of glutathione peroxidase-4 in apolipoprotein E-deficient mice. Free Radic Biol Med 2008, 44:343-352.
93. Draganov D.I., Teiber J.F., Speelman A., Osawa Y., Sunahara R., La Du B.N. Human paraoxonases (PON1, PON2, and PON3) are lactonases with overlapping and distinct substrate specificities. JLipid Res 2005, 46:1239-1247.
94. Mackness M.I., Arrol S., Abbott C., Durrington P.N. Protection of low-density lipoprotein against oxidative modification by high-density lipoprotein associated paraoxonase. Atherosclerosis 1993, 104:129-135.
95. Shih D.M., Gu L., Xia Y.R., Navab M., Li W.F., Hama S., et al. Mice lacking serum paraoxonase are susceptible to organophosphate toxicity and atherosclerosis. Nature 1998, 394:284-287.
96. Tward A., Xia Y.R., Wang X.P., Shi Y.S., Park C., Castellani L.W., et al. Decreased atherosclerotic lesion formation in human serum paraoxonase transgenic mice. Circulation 2002, 106:484-490.
97. Huang Y., Wu Z., Riwanto M., Gao S., Levison B.S., Gu X., et al. Myeloperoxidase, paraoxonase-1, and HDL form a functional ternary complex. JClin Invest 2013, 123:3815-3828.
98. Aharoni S., Aviram M., Fuhrman B. Paraoxonase 1 (PON1) reduces macrophage inflammatory responses. Atherosclerosis 2013, 228:353-361.
99. Mackness M., Mackness B. Targeting paraoxonase-1 in atherosclerosis. Expert Opin Ther Targets 2013, 17:829-837.
100. Aviram M., Vaya J. Paraoxonase 1 activities, regulation, and interactions with atherosclerotic lesion. Curr Opin Lipidol 2013, 24:339-344.
101. Costa L.G., Cole T.B., Furlong C.E. Paraoxonase (PON1): from toxicology to cardiovascular medicine. Acta Biomed 2005, 2(76 Suppl.l):50-57.
102. Ng C.J., Wadleigh D.J., Gangopadhyay A., Hama S., Grijalva V.R., Navab M., et al. Paraoxonase-2 is a ubiquitously expressed protein with antioxidant properties and is capable of preventing cell-mediated oxidative modification of low density lipoprotein. JBiol Chem 2001, 276:44444-44449.
103. Ng C.J., Hama S.Y., Bourquard N., Navab M., Reddy S.T. Adenovirus mediated expression of human paraoxonase 2 protects against the development of atherosclerosis in apolipoprotein E-deficient mice. Mol Genet Metab 2006, 89:368-373.
104. Ng C.J., Bourquard N., Grijalva V., Hama S., Shih D.M., Navab M., et al. Paraoxonase-2 deficiency aggravates atherosclerosis in mice despite lower apolipoprotein-B-containing lipoproteins: anti-atherogenic role for paraoxonase-2. JBiol Chem 2006, 281:29491-29500.
105. Witte I., Foerstermann U., Devarajan A., Reddy S.T., Horke S. Protectors or traitors: the roles of PON2 and PON3 in atherosclerosis and Cancer. JLipids 2012, 2012:342806.
106. Horke S., Witte I., Wilgenbus P., Kruger M., Strand D., Forstermann U. Paraoxonase-2 reduces oxidative stress in vascular cells and decreases endoplasmic reticulum stress-induced caspase activation. Circulation 2007, 115:2055-2064.
107. Hagmann H., Kuczkowski A., Ruehl M., Lamkemeyer T., Brodesser S., Horke S., et al. Breaking the chain at the membrane: paraoxonase 2 counteracts lipid peroxidation at the plasma membrane. FASEB J 2014, 28:1769-1779.
108. Fortunato G., Di Taranto M.D., Bracale U.M., Del Guercio L., Carbone F., Mazzaccara C., et al. Decreased paraoxonase-2 expression in human carotids during the progression of atherosclerosis. Arterioscler Thromb Vasc Biol 2008, 28:594-600.
109. Draganov D.I., Stetson P.L., Watson C.E., Billecke S.S., La Du B.N. Rabbit serum paraoxonase 3 (PON3) is a high density lipoprotein-associated lactonase and protects low density lipoprotein against oxidation. JBiol Chem 2000, 275:33435-33442.
110. Schweikert E.M., Devarajan A., Witte I., Wilgenbus P., Amort J., Forstermann U., et al. PON3 is upregulated in cancer tissues and protects against mitochondrial superoxide-mediated cell death. Cell Death Differ 2012, 19:1549-1560.
111. Shih D.M., Xia Y.R., Wang X.P., Wang S.S., Bourquard N., Fogelman A.M., et al. Decreased obesity and atherosclerosis in human paraoxonase 3 transgenic mice. Circ Res 2007, 100:1200-1207.
112. Marsillach J., Camps J., Beltran-Debon R., Rull A., Aragones G., Maestre-Martinez C., et al. Immunohistochemical analysis of paraoxonases-1 and 3 in human atheromatous plaques. Eur J Clin Invest 2011, 41:308-314.
113. Reny J.L., Combescure C., Daali Y., Fontana P., Group P.O.N.M.-A. Influence of the paraoxonase-1 Q192R genetic variant on clopidogrel responsiveness and recurrent cardiovascular events: a systematic review and meta-analysis. JThromb Haemost 2012, 10:1242-1251.
114. Fefer P., Matetzky S. The genetic basis of platelet responsiveness to clopidogrel. A critical review of the literature. Thromb Haemost 2011, 106:203-210.
115. Riedmaier S., Klein K., Winter S., Hofmann U., Schwab M., Zanger U.M. Paraoxonase (PON1 and PON3) polymorphisms: impact on liver expression and atorvastatin-lactone hydrolysis. Front Pharmacol 2011, 2:41.
116. Griffin P.E., Roddam L.F., Belessis Y.C., Strachan R., Beggs S., Jaffe A., et al. Expression of PPARgamma and paraoxonase 2 correlated with Pseudomonas aeruginosa infection in cystic fibrosis. PLoS One 2012, 7. e42241.
117. Schweikert E.M., Amort J., Wilgenbus P., Forstermann U., Teiber J.F., Horke S. Paraoxonases-2 and -3 are important defense enzymes against Pseudomonas aeruginosa virulence factors due to their anti-oxidative and anti-inflammatory properties. JLipids 2012, 2012:352857.
118. Simanski M., Babucke S., Eberl L., Harder J. Paraoxonase 2 acts as a quorum sensing-quenching factor in human keratinocytes. JInvest Dermatol 2012, 132:2296-2299.
119. Teiber J.F., Horke S., Haines D.C., Chowdhary P.K., Xiao J., Kramer G.L., et al. Dominant role of paraoxonases in inactivation of the Pseudomonas aeruginosa quorum-sensing signal N-(3-oxododecanoyl)-L-homoserine lactone. Infect Immun 2008, 76:2512-2519.
120. Liu V.W., Huang P.L. Cardiovascular roles of nitric oxide: a review of insights from nitric oxide synthase gene disrupted mice. Cardiovasc Res 2008, 77:19-29.
121. Melikian N., Seddon M.D., Casadei B., Chowienczyk P.J., Shah A.M. Neuronal nitric oxide synthase and human vascular regulation. Trends Cardiovasc Med 2009, 19:256-262.
122. Schwarz P.M., Kleinert H., Forstermann U. Potential functional significance of brain-type and muscle-type nitric oxide synthase I expressed in adventitia and media of rat aorta. Arterioscler Thromb Vasc Biol 1999, 19:2584-2590.
123. Tsutsui M. Neuronal nitric oxide synthase as a novel anti-atherogenic factor. JAtheroscler Thromb 2004, 11:41-48.
124. Seddon M.D., Chowienczyk P.J., Brett S.E., Casadei B., Shah A.M. Neuronal nitric oxide synthase regulates basal microvascular tone in humans invivo. Circulation 2008, 117:1991-1996.
125. Seddon M., Melikian N., Dworakowski R., Shabeeh H., Jiang B., Byrne J., et al. Effects of neuronal nitric oxide synthase on human coronary artery diameter and blood flow invivo. Circulation 2009, 119:2656-2662.
126. Kellogg D.L., Zhao J.L., Wu Y. Neuronal nitric oxide synthase control mechanisms in the cutaneous vasculature of humans invivo. JPhysiol 2008, 586:847-857.
127. Kuhlencordt P.J., Hotten S., Schodel J., Rutzel S., Hu K., Widder J., et al. Atheroprotective effects of neuronal nitric oxide synthase in apolipoprotein e knockout mice. Arterioscler Thromb Vasc Biol 2006, 26:1539-1544.
128. Schodel J., Padmapriya P., Marx A., Huang P.L., Ertl G., Kuhlencordt P.J. Expression of neuronal nitric oxide synthase splice variants in atherosclerotic plaques of apoE knockout mice. Atherosclerosis 2009, 206:383-389.
129. Morishita T., Tsutsui M., Shimokawa H., Horiuchi M., Tanimoto A., Suda O., et al. Vasculoprotective roles of neuronal nitric oxide synthase. FASEB J 2002, 16:1994-1996.
130. Pautz A., Art J., Hahn S., Nowag S., Voss C., Kleinert H. Regulation of the expression of inducible nitric oxide synthase. Nitric Oxide 2010, 23:75-93.
131. Gunnett C.A., Lund D.D., McDowell A.K., Faraci F.M., Heistad D.D. Mechanisms of inducible nitric oxide synthase-mediated vascular dysfunction. Arterioscler Thromb Vasc Biol 2005, 25:1617-1622.
132. Chen S.J., Li S.Y., Shih C.C., Liao M.H., Wu C.C. NO contributes to abnormal vascular calcium regulation and reactivity induced by peritonitis-associated septic shock in rats. Shock 2010, 33:473-478.
133. Shelkovnikov S., Gonick H.C. Peroxynitrite but not nitric oxide donors destroys epinephrine: HPLC measurement and rat aorta contractility. Life Sci 2004, 75:2765-2773.
134. Kessler P., Bauersachs J., Busse R., Schini-Kerth V.B. Inhibition of inducible nitric oxide synthase restores endothelium-dependent relaxations in proinflammatory mediator-induced blood vessels. Arterioscler Thromb Vasc Biol 1997, 17:1746-1755.
135. Virdis A., Colucci R., Fornai M., Blandizzi C., Duranti E., Pinto S., et al. Cyclooxygenase-2 inhibition improves vascular endothelial dysfunction in a rat model of endotoxic shock: role of inducible nitric-oxide synthase and oxidative stress. JPharmacol Exp Ther 2005, 312:945-953.
136. Eguchi D., D'Uscio L.V., Wambi C., Weiler D., Kovesdi I., O'Brien T., et al. Inhibitory effect of recombinant iNOS gene expression on vasomotor function of canine basilar artery. Am J Physiol Heart Circ Physiol 2002, 283:H2560-2566.
137. Xia Y., Zweier J.L. Superoxide and peroxynitrite generation from inducible nitric oxide synthase in macrophages. Proc Natl Acad Sci U S A 1997, 94:6954-6958.
138. Marfella R., Di Filippo C., Esposito K., Nappo F., Piegari E., Cuzzocrea S., et al. Absence of inducible nitric oxide synthase reduces myocardial damage during ischemia reperfusion in streptozotocin-induced hyperglycemic mice. Diabetes 2004, 53:454-462.
139. Depre C., Havaux X., Renkin J., Vanoverschelde J.L., Wijns W. Expression of inducible nitric oxide synthase in human coronary atherosclerotic plaque. Cardiovasc Res 1999, 41:465-472.
140. Pacher P., Beckman J.S., Liaudet L. Nitric oxide and peroxynitrite in health and disease. Physiol Rev 2007, 87:315-424.
141. Liaudet L., Rosenblatt-Velin N., Pacher P. Role of peroxynitrite in the cardiovascular dysfunction of septic shock. Curr Vasc Pharmacol 2013, 11:196-207.
142. Wilcox J.N., Subramanian R.R., Sundell C.L., Tracey W.R., Pollock J.S., Harrison D.G., et al. Expression of multiple isoforms of nitric oxide synthase in normal and atherosclerotic vessels. Arterioscler Thromb Vasc Biol 1997, 17:2479-2488.
143. Baker C.S., Hall R.J., Evans T.J., Pomerance A., Maclouf J., Creminon C., et al. Cyclooxygenase-2 is widely expressed in atherosclerotic lesions affecting native and transplanted human coronary arteries and colocalizes with inducible nitric oxide synthase and nitrotyrosine particularly in macrophages. Arterioscler Thromb Vasc Biol 1999, 19:646-655.
144. Kuhlencordt P.J., Chen J., Han F., Astern J., Huang P.L. Genetic deficiency of inducible nitric oxide synthase reduces atherosclerosis and lowers plasma lipid peroxides in apolipoprotein E-knockout mice. Circulation 2001, 103:3099-3104.
145. Li H., Forstermann U. Pharmacological prevention of eNOS Uncoupling. Curr Pharm Des 2014, 20:3595-3606.
146. Kuhlencordt P.J., Gyurko R., Han F., Scherrer-Crosbie M., Aretz T.H., Hajjar R., et al. Accelerated atherosclerosis, aortic aneurysm formation, and ischemic heart disease in apolipoprotein E/endothelial nitric oxide synthase double-knockout mice. Circulation 2001, 104:448-454.
147. Chen J., Kuhlencordt P.J., Astern J., Gyurko R., Huang P.L. Hypertension does not account for the accelerated atherosclerosis and development of aneurysms in male apolipoprotein e/endothelial nitric oxide synthase double knockout mice. Circulation 2001, 104:2391-2394.
148. Ozaki M., Kawashima S., Yamashita T., Hirase T., Namiki M., Inoue N., et al. Overexpression of endothelial nitric oxide synthase accelerates atherosclerotic lesion formation in apoE-deficient mice. JClin Invest 2002, 110:331-340.
149. Takaya T., Hirata K., Yamashita T., Shinohara M., Sasaki N., Inoue N., et al. Aspecific role for eNOS-derived reactive oxygen species in atherosclerosis progression. Arterioscler Thromb Vasc Biol 2007, 27:1632-1637.
150. Ponnuswamy P., Schrottle A., Ostermeier E., Gruner S., Huang P.L., Ertl G., et al. eNOS protects from atherosclerosis despite relevant superoxide production by the enzyme in apoE mice. PLoS One 2012, 7:e30193.
151. Kauser K., da Cunha V., Fitch R., Mallari C., Rubanyi G.M. Role of endogenous nitric oxide in progression of atherosclerosis in apolipoprotein E-deficient mice. Am J Physiol Heart Circ Physiol 2000, 278:H1679-1685.
152. Vendrov A.E., Hakim Z.S., Madamanchi N.R., Rojas M., Madamanchi C., Runge M.S. Atherosclerosis is attenuated by limiting superoxide generation in both macrophages and vessel wall cells. Arterioscler Thromb Vasc Biol 2007, 27:2714-2721.
153. Borissoff J.I., Heeneman S., Kilinc E., Kassak P., Van Oerle R., Winckers K., et al. Early atherosclerosis exhibits an enhanced procoagulant state. Circulation 2010, 122:821-830.
154. Rowley J.W., Oler A.J., Tolley N.D., Hunter B.N., Low E.N., Nix D.A., et al. Genome-wide RNA-seq analysis of human and mouse platelet transcriptomes. Blood 2011, 118:e101-111.
155. Violi F., Pignatelli P. Platelet NOX, a novel target for anti-thrombotic treatment. Thromb Haemost 2014, 111:817-823.
156. Cahilly C., Ballantyne C.M., Lim D.S., Gotto A., Marian A.J. Avariant of p22(phox), involved in generation of reactive oxygen species in the vessel wall, is associated with progression of coronary atherosclerosis. Circ Res 2000, 86:391-395.
157. Andreassi M.G., Adlerstein D., Carpeggiani C., Shehi E., Fantinato S., Ghezzi E., et al. Individual and summed effects of high-risk genetic polymorphisms on recurrent cardiovascular events following ischemic heart disease. Atherosclerosis 2012, 223:409-415.
158. Arca M., Conti B., Montali A., Pignatelli P., Campagna F., Barilla F., et al. C242T polymorphism of NADPH oxidase p22phox and recurrence of cardiovascular events in coronary artery disease. Arterioscler Thromb Vasc Biol 2008, 28:752-757.
159. Kakko S., Paivansalo M., Koistinen P., Kesaniemi Y.A., Kinnula V.L., Savolainen M.J. The signal sequence polymorphism of the MnSOD gene is associated with the degree of carotid atherosclerosis. Atherosclerosis 2003, 168:147-152.
160. Fujimoto H., Taguchi J., Imai Y., Ayabe S., Hashimoto H., Kobayashi H., et al. Manganese superoxide dismutase polymorphism affects the oxidized low-density lipoprotein-induced apoptosis of macrophages and coronary artery disease. Eur Heart J 2008, 29:1267-1274.
161. Marklund S.L., Nilsson P., Israelsson K., Schampi I., Peltonen M., Asplund K. Two variants of extracellular-superoxide dismutase: relationship to cardiovascular risk factors in an unselected middle-aged population. JIntern Med 1997, 242:5-14.
162. Juul K., Tybjaerg-Hansen A., Marklund S., Heegaard N.H., Steffensen R., Sillesen H., et al. Genetically reduced antioxidative protection and increased ischemic heart disease risk: the Copenhagen City Heart Study. Circulation 2004, 109:59-65.
163. Hamanishi T., Furuta H., Kato H., Doi A., Tamai M., Shimomura H., et al. Functional variants in the glutathione peroxidase-1 (GPx-1) gene are associated with increased intima-media thickness of carotid arteries and risk of macrovascular diseases in japanese type 2 diabetic patients. Diabetes 2004, 53:2455-2460.
164. Heslop C.L., Tebbutt S.J., Podder M., Ruan J., Hill J.S. Combined polymorphisms in oxidative stress genes predict coronary artery disease and oxidative stress in coronary angiography patients. Ann Hum Genet 2012, 76:435-447.
165. Halliwell B. The antioxidant paradox: less paradoxical now?. Br J Clin Pharmacol 2013, 75:637-644.
166. Bjelakovic G., Nikolova D., Gluud L.L., Simonetti R.G., Gluud C. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAm Med Assoc 2007, 297:842-857.
167. Touyz R.M. Reactive oxygen species, vascular oxidative stress, and redox signaling in hypertension: what is the clinical significance?. Hypertension 2004, 44:248-252.
168. Bast A., Haenen G.R. Ten misconceptions about antioxidants. Trends Pharmacol Sci 2013, 34:430-436.
169. Milman U., Blum S., Shapira C., Aronson D., Miller-Lotan R., Anbinder Y., et al. Vitamin E supplementation reduces cardiovascular events in a subgroup of middle-aged individuals with both type 2 diabetes mellitus and the haptoglobin 2-2 genotype: a prospective double-blinded clinical trial. Arterioscler Thromb Vasc Biol 2008, 28:341-347.
170. Blum S., Vardi M., Levy N.S., Miller-Lotan R., Levy A.P. The effect of vitamin E supplementation on cardiovascular risk in diabetic individuals with different haptoglobin phenotypes. Atherosclerosis 2010, 211:25-27.
171. Chandel N.S., Tuveson D.A. The promise and perils of antioxidants for cancer patients. NEngl J Med 2014, 371:177-178.