Impact of Oxidative Stress on the Heart and Vasculature: Part 2 of a 3-Part Series

Journal of the American College of Cardiology

Volumn 70, Issue 2, 2017, Pages 212-229

  Münzel, Thomas ^a   Camici, Giovanni G ^b   Maack, Christoph ^c   Bonetti, Nicole R ^b   Fuster, Valentin ^d,e   Kovacic, Jason C ^d  

^a UNIVERSITY MEDICAL CENTER MAINZ   (Germany)

^b UNIVERSITY OF ZURICH   (Switzerland)

^c SAARLAND UNIVERSITY   (Germany)

^d MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^e CENTRO NACIONAL DE INVESTIGACIONES CARDIOVASCULARES CNIC   (Spain)

Author keywords

cardiac; reactive oxygen species; vascular

Indexed keywords

7 CHLORO 5 (2 CHLOROPHENYL) 1,5 DIHYDRO 4,1 BENZOTHIAZEPIN 2(3H) ONE; ACETYLSALICYLIC ACID; ANGIOTENSIN 1 RECEPTOR ANTAGONIST; APOCYNIN; ARYLDIALKYLPHOSPHATASE; CATALASE; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; ELAMIPRETIDE; ENDOTHELIAL NITRIC OXIDE SYNTHASE; EXTRACELLULAR SUPEROXIDE DISMUTASE; GLUTATHIONE PEROXIDASE; GUANOSINE TRIPHOSPHATE CYCLOHYDROLASE I; HEME OXYGENASE; HYDRALAZINE; NITRIC OXIDE SYNTHASE; OXIDOREDUCTASE INHIBITOR; PROBUCOL; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE; SUPEROXIDE; SUPEROXIDE DISMUTASE; THIOREDOXIN; VITAMIN; XANTHINE OXIDASE;

ACUTE HEART INFARCTION; ATHEROSCLEROSIS; CARDIOVASCULAR RISK; CLINICAL OUTCOME; DISORDERS OF MITOCHONDRIAL FUNCTIONS; ENDOTHELIAL DYSFUNCTION; GENE THERAPY; HEART ARRHYTHMIA; HEART DEATH; HEART FAILURE; HEART LEFT VENTRICLE FAILURE; HEART VENTRICLE REMODELING; HUMAN; MITOCHONDRION; MOLECULAR INTERACTION; NECROSIS; NONHUMAN; OXIDATION REDUCTION REACTION; OXIDATIVE STRESS; PATHOPHYSIOLOGY; PRIORITY JOURNAL; REVIEW; VASCULAR DISEASE; VASCULAR REMODELING; VITAMIN SUPPLEMENTATION; ANIMAL; APOPTOSIS; CARDIAC MUSCLE; METABOLISM; PATHOLOGY; PHYSIOLOGY; SIGNAL TRANSDUCTION; VASCULAR SMOOTH MUSCLE;

ANIMALS; APOPTOSIS; HEART FAILURE; HUMANS; MUSCLE, SMOOTH, VASCULAR; MYOCARDIUM; OXIDATIVE STRESS; REACTIVE OXYGEN SPECIES; SIGNAL TRANSDUCTION;

EID: 85029429291     PISSN: 07351097     EISSN: 15583597     Source Type: Journal    
DOI: 10.1016/j.jacc.2017.05.035     Document Type: Review

References (167)

1. Gori, T., Münzel, T., Oxidative stress and endothelial dysfunction: therapeutic implications. Ann Med 43 (2011), 259–272.
2. Münzel, T., Gori, T., Bruno, R.M., Taddei, S., Is oxidative stress a therapeutic target in cardiovascular disease?. Eur Heart J 31 (2010), 2741–2748.
3. Maack, C., Kartes, T., Kilter, H., et al. Oxygen free radical release in human failing myocardium is associated with increased activity of rac1-GTPase and represents a target for statin treatment. Circulation 108 (2003), 1567–1574.
4. Mollnau, H., Oelze, M., August, M., et al. Mechanisms of increased vascular superoxide production in an experimental model of idiopathic dilated cardiomyopathy. Arterioscler Thromb Vasc Biol 25 (2005), 2554–2559.
5. Belch, J.J., Bridges, A.B., Scott, N., Chopra, M., Oxygen free radicals and congestive heart failure. Br Heart J 65 (1991), 245–248.
6. Burgoyne, J.R., Mongue-Din, H., Eaton, P., Shah, A.M., Redox signaling in cardiac physiology and pathology. Circ Res 111 (2012), 1091–1106.
7. Wagner, S., Rokita, A.G., Anderson, M.E., Maier, L.S., Redox regulation of sodium and calcium handling. Antioxid Redox Signal 18 (2013), 1063–1077.
8. Kröller-Schön, S., Steven, S., Kossmann, S., et al. Molecular mechanisms of the crosstalk between mitochondria and NADPH oxidase through reactive oxygen species-studies in white blood cells and in animal models. Antioxid Redox Signal 20 (2014), 247–266.
9. Maack, C., Böhm, M., Targeting mitochondrial oxidative stress in heart failure throttling the afterburner. J Am Coll Cardiol 58 (2011), 83–86.
10. Lassègue, B., San Martín, A., Griendling, K.K., Biochemistry, physiology, and pathophysiology of NADPH oxidases in the cardiovascular system. Circ Res 110 (2012), 1364–1390.
11. Prosser, B.L., Ward, C.W., Lederer, W.J., X-ROS signaling: rapid mechano-chemo transduction in heart. Science 333 (2011), 1440–1445.
12. Jian, Z., Han, H., Zhang, T., et al. Mechanochemotransduction during cardiomyocyte contraction is mediated by localized nitric oxide signaling. Sci Signal, 7, 2014, ra27.
13. Wenzel, P., Knorr, M., Kossmann, S., et al. Lysozyme M-positive monocytes mediate angiotensin II-induced arterial hypertension and vascular dysfunction. Circulation 124 (2011), 1370–1381.
14. Kuroda, J., Ago, T., Matsushima, S., Zhai, P., Schneider, M.D., Sadoshima, J., NADPH oxidase 4 (Nox4) is a major source of oxidative stress in the failing heart. Proc Natl Acad Sci U S A 107 (2010), 15565–15570.
15. Matsushima, S., Kuroda, J., Ago, T., et al. Broad suppression of NADPH oxidase activity exacerbates ischemia/reperfusion injury through inadvertent downregulation of hypoxia-inducible factor-1α and upregulation of peroxisome proliferator-activated receptor-α. Circ Res 112 (2013), 1135–1149.
16. Craige, S.M., Chen, K., Pei, Y., et al. NADPH oxidase 4 promotes endothelial angiogenesis through endothelial nitric oxide synthase activation. Circulation 124 (2011), 731–740.
17. Zhang, M., Brewer, A.C., Schröder, K., et al. NADPH oxidase-4 mediates protection against chronic load-induced stress in mouse hearts by enhancing angiogenesis. Proc Natl Acad Sci U S A 107 (2010), 18121–18126.
18. Ide, T., Tsutsui, H., Kinugawa, S., et al. Direct evidence for increased hydroxyl radicals originating from superoxide in the failing myocardium. Circ Res 86 (2000), 152–157.
19. Aon, M.A., Cortassa, S., O'Rourke, B., Redox-optimized ROS balance: a unifying hypothesis. Biochim Biophys Acta 1797 (2010), 865–877.
20. Nickel, A., Kohlhaas, M., Maack, C., Mitochondrial reactive oxygen species production and elimination. J Mol Cell Cardiol 73 (2014), 26–33.
21. Nickel, A.G., von Hardenberg, A., Hohl, M., et al. Reversal of mitochondrial transhydrogenase causes oxidative stress in heart failure. Cell Metab 22 (2015), 472–484.
22. Dai, D.F., Hsieh, E.J., Liu, Y., et al. Mitochondrial proteome remodelling in pressure overload-induced heart failure: the role of mitochondrial oxidative stress. Cardiovasc Res 93 (2012), 79–88.
23. Dai, D.F., Johnson, S.C., Villarin, J.J., et al. Mitochondrial oxidative stress mediates angiotensin II-induced cardiac hypertrophy and Gαq overexpression-induced heart failure. Circ Res 108 (2011), 837–846.
24. Hornig, B., Arakawa, N., Kohler, C., Drexler, H., Vitamin C improves endothelial function of conduit arteries in patients with chronic heart failure. Circulation 97 (1998), 363–368.
25. Förstermann, U., Münzel, T., Endothelial nitric oxide synthase in vascular disease: from marvel to menace. Circulation 113 (2006), 1708–1714.
26. Lee, B.E., Toledo, A.H., Anaya-Prado, R., Roach, R.R., Toledo-Pereyra, L.H., Allopurinol, xanthine oxidase, and cardiac ischemia. J Investig Med 57 (2009), 902–909.
27. Baldus, S., Müllerleile, K., Chumley, P., et al. Inhibition of xanthine oxidase improves myocardial contractility in patients with ischemic cardiomyopathy. Free Radic Biol Med 41 (2006), 1282–1288.
28. Hare, J.M., Mangal, B., Brown, J., et al., for the OPT-CHF Investigators. Impact of oxypurinol in patients with symptomatic heart failure. Results of the OPT-CHF study. J Am Coll Cardiol 51 (2008), 2301–2309.
29. Dai, D.F., Chen, T., Szeto, H., et al. Mitochondrial targeted antioxidant peptide ameliorates hypertensive cardiomyopathy. J Am Coll Cardiol 58 (2011), 73–82.
30. Keaney, J.F. Jr., Gaziano, J.M., Xu, A., et al. Low-dose alpha-tocopherol improves and high-dose alpha-tocopherol worsens endothelial vasodilator function in cholesterol-fed rabbits. J Clin Invest 93 (1994), 844–851.
31. Stocker, R., The ambivalence of vitamin E in atherogenesis. Trends Biochem Sci 24 (1999), 219–223.
32. Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med 342 (2000), 145–153.
33. Lonn, E., Bosch, J., Yusuf, S., et al., HOPE and HOPE-TOO Trial Investigators. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA 293 (2005), 1338–1347.
34. Smith, R.A., Hartley, R.C., Cochemé H.M., Murphy, M.P., Mitochondrial pharmacology. Trends Pharmacol Sci 33 (2012), 341–352.
35. Szeto, H.H., First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics. Br J Pharmacol 171 (2014), 2029–2050.
36. Sparagna, G.C., Lesnefsky, E.J., Cardiolipin remodeling in the heart. J Cardiovasc Pharmacol 53 (2009), 290–301.
37. Brown, D.A., Hale, S.L., Baines, C.P., et al. Reduction of early reperfusion injury with the mitochondria-targeting peptide bendavia. J Cardiovasc Pharmacol Ther 19 (2014), 121–132.
38. Gibson, C.M., Giugliano, R.P., Kloner, R.A., et al. EMBRACE STEMI study: a Phase 2a trial to evaluate the safety, tolerability, and efficacy of intravenous MTP-131 on reperfusion injury in patients undergoing primary percutaneous coronary intervention. Eur Heart J 37 (2016), 1296–1303.
39. 2+ exchange prevents sudden death in a guinea pig model of heart failure. Circ Res 115 (2014), 44–54.
40. + redox balance as a therapy for heart failure. Circulation 134 (2016), 883–894.
41. Koentges, C., Bode, C., Bugger, H., SIRT3 in cardiac physiology and disease. Front Cardiovasc Med, 3, 2016, 38.
42. Rajasekaran, N.S., Connell, P., Christians, E.S., et al. Human αB-crystallin mutation causes oxido-reductive stress and protein aggregation cardiomyopathy in mice. Cell 130 (2007), 427–439.
43. Münzel, T., Keaney, J.F. Jr., Are ACE inhibitors a “magic bullet” against oxidative stress?. Circulation 104 (2001), 1571–1574.
44. Hare, J.M., Nitroso-redox balance in the cardiovascular system. N Engl J Med 351 (2004), 2112–2114.
45. Münzel, T., Daiber, A., Gori, T., More answers to the still unresolved question of nitrate tolerance. Eur Heart J 34 (2013), 2666–2673.
46. Daiber, A., Oelze, M., Coldewey, M., et al. Hydralazine is a powerful inhibitor of peroxynitrite formation as a possible explanation for its beneficial effects on prognosis in patients with congestive heart failure. Biochem Biophys Res Commu 338 (2005), 1865–1874.
47. Münzel, T., Kurz, S., Rajagopalan, S., et al. Hydralazine prevents nitroglycerin tolerance by inhibiting activation of a membrane-bound NADH oxidase. A new action for an old drug. J Clin Invest 98 (1996), 1465–1470.
48. Dulce, R.A., Yiginer, O., Gonzalez, D.R., et al. Hydralazine and organic nitrates restore impaired excitation-contraction coupling by reducing calcium leak associated with nitroso-redox imbalance. J Biol Chem 288 (2013), 6522–6533.
49. Münzel, T., Steven, S., Daiber, A., Organic nitrates: update on mechanisms underlying vasodilation, tolerance and endothelial dysfunction. Vascul Pharmacol 63 (2014), 105–113.
50. Taylor, A.L., Ziesche, S., Yancy, C., et al., African-American Heart Failure Trial Investigators. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med 351 (2004), 2049–2057.
51. Hulsmans, M., Holvoet, P., The vicious circle between oxidative stress and inflammation in atherosclerosis. J Cell Mol Med 14 (2010), 70–78.
52. Madamanchi, N.R., Hakim, Z.S., Runge, M.S., Oxidative stress in atherogenesis and arterial thrombosis: the disconnect between cellular studies and clinical outcomes. J Thromb Haemost 3 (2005), 254–267.
53. Freed, J.K., Gutterman, D.D., Mitochondrial reactive oxygen species and vascular function: less is more. Arterioscler Thromb Vasc Biol 33 (2013), 673–675.
54. Stocker, R., Keaney, J.F. Jr., Role of oxidative modifications in atherosclerosis. Physiol Rev 84 (2004), 1381–1478.
55. Griendling, K.K., Sorescu, D., Lassègue, B., Ushio-Fukai, M., Modulation of protein kinase activity and gene expression by reactive oxygen species and their role in vascular physiology and pathophysiology. Arterioscler Thromb Vasc Biol 20 (2000), 2175–2183.
56. Förstermann, U., Nitric oxide and oxidative stress in vascular disease. Pflugers Archiv 459 (2010), 923–939.
57. Gryglewski, R.J., Palmer, R.M., Moncada, S., Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor. Nature 320 (1986), 454–456.
58. Beckman, J.S., Oxidative damage and tyrosine nitration from peroxynitrite. Chem Res Toxicol 9 (1996), 836–844.
59. Beckman, J.S., Koppenol, W.H., Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol 271 (1996), C1424–C1437.
60. Laursen, J.B., Somers, M., Kurz, S., et al. Endothelial regulation of vasomotion in apoE-deficient mice: implications for interactions between peroxynitrite and tetrahydrobiopterin. Circulation 103 (2001), 1282–1288.
61. Harrison, D.G., Chen, W., Dikalov, S., Li, L., Regulation of endothelial cell tetrahydrobiopterin pathophysiological and therapeutic implications. Adv Pharmacol 60 (2010), 107–132.
62. Li, H., Horke, S., Förstermann, U., Vascular oxidative stress, nitric oxide and atherosclerosis. Atherosclerosis 237 (2014), 208–219.
63. 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 10 (2011), 453–471.
64. Dikalova, A., Clempus, R., Lassègue, B., et al. Nox1 overexpression potentiates angiotensin II-induced hypertension and vascular smooth muscle hypertrophy in transgenic mice. Circulation 112 (2005), 2668–2676.
65. Matsuno, K., Yamada, H., Iwata, K., et al. Nox1 is involved in angiotensin II-mediated hypertension: a study in Nox1-deficient mice. Circulation 112 (2005), 2677–2685.
66. −/− mice. J Clin Invest 108 (2001), 1513–1522.
67. phox in vascular oxidative stress and hypertension caused by angiotensin II. Hypertension 40 (2002), 511–515.
68. Guzik, T.J., Sadowski, J., Guzik, B., et al. Coronary artery superoxide production and nox isoform expression in human coronary artery disease. Arterioscler Thromb Vasc Biol 26 (2006), 333–339.
69. Landmesser, U., Spiekermann, S., Preuss, C., et al. Angiotensin II induces endothelial xanthine oxidase activation: role for endothelial dysfunction in patients with coronary disease. Arterioscler Thromb Vasc Biol 27 (2007), 943–948.
70. White, C.R., Darley-Usmar, V., Berrington, W.R., et al. Circulating plasma xanthine oxidase contributes to vascular dysfunction in hypercholesterolemic rabbits. Proc Natl Acad Sci U S A 93 (1996), 8745–8749.
71. Guthikonda, S., Sinkey, C., Barenz, T., Haynes, W.G., Xanthine oxidase inhibition reverses endothelial dysfunction in heavy smokers. Circulation 107 (2003), 416–421.
72. Schröder, K., Vecchione, C., Jung, O., et al. Xanthine oxidase inhibitor tungsten prevents the development of atherosclerosis in ApoE knockout mice fed a Western-type diet. Free Radic Biol Med 41 (2006), 1353–1360.
73. Ramachandran, A., Levonen, A.L., Brookes, P.S., et al. Mitochondria, nitric oxide, and cardiovascular dysfunction. Free Radic Biol Med 33 (2002), 1465–1474.
74. Ballinger, S.W., Patterson, C., Knight-Lozano, C.A., et al. Mitochondrial integrity and function in atherogenesis. Circulation 106 (2002), 544–549.
75. Zeini, M., López-Fontal, R., Través, P.G., Benito, G., Hortelano, S., Differential sensitivity to apoptosis among the cells that contribute to the atherosclerotic disease. Biochem Biophys Res Comm 363 (2007), 444–450.
76. Ohashi, M., Runge, M.S., Faraci, F.M., Heistad, D.D., MnSOD deficiency increases endothelial dysfunction in ApoE-deficient mice. Arterioscler Thromb Vasc Biol 26 (2006), 2331–2336.
77. 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 25 (2005), 1617–1622.
78. 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 33 (2010), 473–478.
79. Shelkovnikov, S., Gonick, H.C., Peroxynitrite but not nitric oxide donors destroys epinephrine: HPLC measurement and rat aorta contractility. Life Sci 75 (2004), 2765–2773.
80. Virdis, A., Colucci, R., Fornai, M., 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. J Pharmacol Exp Ther 312 (2005), 945–953.
81. 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 17 (1997), 1746–1755.
82. Eguchi, D., D'Uscio, L.V., Wambi, C., et al. Inhibitory effect of recombinant iNOS gene expression on vasomotor function of canine basilar artery. Am J Physiol Heart Circ Physiol 283 (2002), H2560–H2566.
83. Marfella, R., Di Filippo, C., Esposito, K., et al. Absence of inducible nitric oxide synthase reduces myocardial damage during ischemia reperfusion in streptozotocin-induced hyperglycemic mice. Diabetes 53 (2004), 454–462.
84. 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 103 (2001), 3099–3104.
85. Ravalli, S., Albala, A., Ming, M., et al. Inducible nitric oxide synthase expression in smooth muscle cells and macrophages of human transplant coronary artery disease. Circulation 97 (1998), 2338–2345.
86. Tribble, D.L., Gong, E.L., Leeuwenburgh, C., et al. Fatty streak formation in fat-fed mice expressing human copper-zinc superoxide dismutase. Arterioscler Thromb Vasc Biol 17 (1997), 1734–1740.
87. Yang, H., Roberts, L.J., Shi, M.J., et al. Retardation of atherosclerosis by overexpression of catalase or both Cu/Zn-superoxide dismutase and catalase in mice lacking apolipoprotein E. Circ Res 95 (2004), 1075–1081.
88. Fukai, T., Ushio-Fukai, M., Superoxide dismutases: role in redox signaling, vascular function, and diseases. Antioxid Redox Signal 15 (2011), 1583–1606.
89. Sentman, M.L., Brännstrom, T., Westerlund, S., et al. Extracellular superoxide dismutase deficiency and atherosclerosis in mice. Arterioscler Thromb Vasc Biol 21 (2001), 1477–1482.
90. 2 . Hypertension 46 (2005), 732–737.
91. Yang, H., Zhou, L., Wang, Z., et al. Overexpression of antioxidant enzymes in ApoE-deficient mice suppresses benzo(a)pyrene-accelerated atherosclerosis. Atherosclerosis 207 (2009), 51–58.
92. Witte, I., Foerstermann, U., Devarajan, A., Reddy, S.T., Horke, S., Protectors or traitors: the roles of PON2 and PON3 in atherosclerosis and cancer. J Lipids, 2012, 2012, 342806.
93. Huang, Y., Wu, Z., Riwanto, M., et al. Myeloperoxidase, paraoxonase-1, and HDL form a functional ternary complex. J Clin Invest 123 (2013), 3815–3828.
94. Horke, S., Witte, I., Wilgenbus, P., Krüger, M., Strand, D., Förstermann, U., Paraoxonase-2 reduces oxidative stress in vascular cells and decreases endoplasmic reticulum stress-induced caspase activation. Circulation 115 (2007), 2055–2064.
95. Ng, C.J., Bourquard, N., Grijalva, V., et al. Paraoxonase-2 deficiency aggravates atherosclerosis in mice despite lower apolipoprotein-B-containing lipoproteins: anti-atherogenic role for paraoxonase-2. J Biol Chem 281 (2006), 29491–29500.
96. Altenhöfer, S., Witte, I., Teiber, J.F., et al. One enzyme, two functions: PON2 prevents mitochondrial superoxide formation and apoptosis independent from its lactonase activity. J Biol Chem 285 (2010), 24398–24403.
97. Devarajan, A., Bourquard, N., Hama, S., et al. Paraoxonase 2 deficiency alters mitochondrial function and exacerbates the development of atherosclerosis. Antioxid Redox Signal 14 (2011), 341–351.
98. Fortunato, G., Di Taranto, M.D., Bracale, U.M., et al. Decreased paraoxonase-2 expression in human carotids during the progression of atherosclerosis. Arterioscler Thromb Vasc Biol 28 (2008), 594–600.
99. Schweikert, E.M., Devarajan, A., Witte, I., et al. PON3 is upregulated in cancer tissues and protects against mitochondrial superoxide-mediated cell death. Cell Death Differ 19 (2012), 1549–1560.
100. Shih, D.M., Xia, Y.R., Wang, X.P., et al. Decreased obesity and atherosclerosis in human paraoxonase 3 transgenic mice. Circ Res 100 (2007), 1200–1207.
101. Marsillach, J., Camps, J., Beltran-Debón, R., et al. Immunohistochemical analysis of paraoxonases-1 and 3 in human atheromatous plaques. Eur J Clin Invest 41 (2011), 308–314.
102. Lewis, P., Stefanovic, N., Pete, J., et al. Lack of the antioxidant enzyme glutathione peroxidase-1 accelerates atherosclerosis in diabetic apolipoprotein E-deficient mice. Circulation 115 (2007), 2178–2187.
103. Torzewski, M., Ochsenhirt, V., Kleschyov, A.L., et al. Deficiency of glutathione peroxidase-1 accelerates the progression of atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 27 (2007), 850–857.
104. Yoshida, T., Maulik, N., Engelman, R.M., et al. Glutathione peroxidase knockout mice are susceptible to myocardial ischemia reperfusion injury. Circulation 96 (1997), II216–II220.
105. Blankenberg, S., Rupprecht, H.J., Bickel, C., et al., AtheroGene Investigators. Glutathione peroxidase 1 activity and cardiovascular events in patients with coronary artery disease. N Engl J Med 349 (2003), 1605–1613.
106. Guo, Z., Ran, Q., Roberts, L.J. II, et al. Suppression of atherogenesis by overexpression of glutathione peroxidase-4 in apolipoprotein E-deficient mice. Free Radic Biol Med 44 (2008), 343–352.
107. Stocker, R., Perrella, M.A., Heme oxygenase-1: a novel drug target for atherosclerotic diseases?. Circulation 114 (2006), 2178–2189.
108. Jiang, F., Roberts, S.J., Datla Sr., Dusting, G.J., NO modulates NADPH oxidase function via heme oxygenase-1 in human endothelial cells. Hypertension 48 (2006), 950–957.
109. Taille, C., El-Benna, J., Lanone, S., et al. Induction of heme oxygenase-1 inhibits NAD(P)H oxidase activity by down-regulating cytochrome b558 expression via the reduction of heme availability. J Biol Chem 279 (2004), 28681–28688.
110. Hoekstra, K.A., Godin, D.V., Cheng, K.M., Protective role of heme oxygenase in the blood vessel wall during atherogenesis. Biochem Cell Biol 82 (2004), 351–359.
111. Hilgers, R.H., Kundumani-Sridharan, V., Subramani, J., et al. Thioredoxin reverses age-related hypertension by chronically improving vascular redox and restoring eNOS function. Sci Transl Med, 9, 2017, eaaf6094.
112. May, J.M., How does ascorbic acid prevent endothelial dysfunction?. Free Radic Biol Med 28 (2000), 1421–1429.
113. Heller, R., Unbehaun, A., Schellenberg, B., Mayer, B., Werner-Felmayer, G., Werner, E.R., L-Ascorbic acid potentiates endothelial nitric oxide synthesis via a chemical stabilization of tetrahydrobiopterin. J Biol Chem 276 (2001), 40–47.
114. Wallerath, T., Deckert, G., Ternes, T., et al. Resveratrol, a polyphenolic phytoalexin present in red wine, enhances expression and activity of endothelial nitric oxide synthase. Circulation 106 (2002), 1652–1658.
115. Wallerath, T., Li, H., Gödtel-Ambrust, U., Schwarz, P.M., Förstermann, U., A blend of polyphenolic compounds explains the stimulatory effect of red wine on human endothelial NO synthase. Nitric Oxide 12 (2005), 97–104.
116. Evrard, S.M., Lecce, L., Michelis, K.C., et al. Endothelial to mesenchymal transition is common in atherosclerotic lesions and is associated with plaque instability. Nat Commun, 7, 2016, 11853.
117. Kunsch, C., Medford, R.M., Oxidative stress as a regulator of gene expression in the vasculature. Circ Res 85 (1999), 753–766.
118. Stocker, R., Keaney, J.F. Jr., New insights on oxidative stress in the artery wall. J Thromb Haemost 3 (2005), 1825–1834.
119. Kovacic, J.C., Mercader, N., Torres, M., Boehm, M., Fuster, V., Epithelial-to-mesenchymal and endothelial-to-mesenchymal transition: from cardiovascular development to disease. Circulation 125 (2012), 1795–1808.
120. 1 -type angiotensin receptor in oxidative stress and atherogenesis: part I: oxidative stress and atherogenesis. Circulation 105 (2002), 393–396.
121. Zalba, G., San José G., Moreno, M.U., et al. Oxidative stress in arterial hypertension: role of NAD(P)H oxidase. Hypertension 38 (2001), 1395–1399.
122. Laufs, U., Kilter, H., Konkol, C., Wassmann, S., Böhm, M., Nickenig, G., Impact of HMG CoA reductase inhibition on small GTPases in the heart. Cardiovasc Res 53 (2002), 911–920.
123. Touyz, R.M., Yao, G., Schiffrin, E.L., c-Src induces phosphorylation and translocation of p47phox: role in superoxide generation by angiotensin II in human vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 23 (2003), 981–987.
124. Grote, K., Flach, I., Luchtefeld, M., et al. Mechanical stretch enhances mRNA expression and proenzyme release of matrix metalloproteinase-2 (MMP-2) via NAD(P)H oxidase-derived reactive oxygen species. Circ Res 92 (2003), e80–e86.
125. Shc mediates hypertension-associated, cyclic stretch-dependent, endothelial damage. Hypertension 64 (2014), 347–353.
126. Li, H., Witte, K., August, M., et al. Reversal of endothelial nitric oxide synthase uncoupling and up-regulation of endothelial nitric oxide synthase expression lowers blood pressure in hypertensive rats. J Am Coll Cardiol 47 (2006), 2536–2544.
127. Shc adaptor protein prevents hyperglycemia-induced endothelial dysfunction and oxidative stress. Proc Natl Acad Sci U S A 104 (2007), 5217–5222.
128. Giacco, F., Brownlee, M., Oxidative stress and diabetic complications. Circ Res 107 (2010), 1058–1070.
129. Funk, S.D., Yurdagul, A. Jr., Orr, A.W., Hyperglycemia and endothelial dysfunction in atherosclerosis: lessons from type 1 diabetes. Int J Vasc Med, 2012, 2012, 569654.
130. Hink, U., Li, H., Mollnau, H., et al. Mechanisms underlying endothelial dysfunction in diabetes mellitus. Circ Res 88 (2001), E14–E22.
131. Chalupsky, K., Cai, H., Endothelial dihydrofolate reductase: critical for nitric oxide bioavailability and role in angiotensin II uncoupling of endothelial nitric oxide synthase. Proc Natl Acad Sci U S A 102 (2005), 9056–9061.
132. Pritchard, K.A. Jr., Groszek, L., Smalley, D.M., et al. Native low-density lipoprotein increases endothelial cell nitric oxide synthase generation of superoxide anion. Circ Res 77 (1995), 510–518.
133. Stepp, D.W., Ou, J., Ackerman, A.W., Welak, S., Klick, D., Pritchard, K.A. Jr., Native LDL and minimally oxidized LDL differentially regulate superoxide anion in vascular endothelium in situ. Am J Physiol Heart Circ Physiol 283 (2002), H750–H759.
134. Stroes, E., Kastelein, J., Cosentino, F., et al. Tetrahydrobiopterin restores endothelial function in hypercholesterolemia. J Clin Invest 99 (1997), 41–46.
135. Xia, N., Daiber, A., Habermeier, A., et al. Resveratrol reverses endothelial nitric-oxide synthase uncoupling in apolipoprotein E knockout mice. J Pharmacol Exp Ther 335 (2010), 149–154.
136. Ylä-Herttuala, S., Rosenfeld, M.E., Parthasarathy, S., et al. Gene expression in macrophage-rich human atherosclerotic lesions. 15-Lipoxygenase and acetyl low density lipoprotein receptor messenger RNA colocalize with oxidation specific lipid-protein adducts. J Clin Invest 87 (1991), 1146–1152.
137. Nickenig, G., Bäumer, A.T., Temur, Y., Kebben, D., Jockenhövel, F., Böhm, M., Statin-sensitive dysregulated AT1 receptor function and density in hypercholesterolemic men. Circulation 100 (1999), 2131–2134.
138. Camici, G.G., Savarese, G., Akhmedov, A., Lüscher, T.F., Molecular mechanism of endothelial and vascular aging: implications for cardiovascular disease. Eur Heart J 36 (2015), 3392–3403.
139. Donato, A.J., Gano, L.B., Eskurza, I., et al. Vascular endothelial dysfunction with aging: endothelin-1 and endothelial nitric oxide synthase. Am J Physiol Heart Circ Physiol 297 (2009), H425–H432.
140. Lüscher, T.F., Yang, Z.H., Diederich, D., Bühler, F.R., Endothelium-derived vasoactive substances: potential role in hypertension, atherosclerosis, and vascular occlusion. J Cardiovasc Pharmacol 14:Suppl 6 (1989), S63–S69.
141. van der Loo, B., Labugger, R., Skepper, J.N., et al. Enhanced peroxynitrite formation is associated with vascular aging. J Exp Med 192 (2000), 1731–1744.
142. Yang, Y.M., Huang, A., Kaley, G., Sun, D., eNOS uncoupling and endothelial dysfunction in aged vessels. Am J Physiol Heart Circ Physiol 297 (2009), H1829–H1836.
143. Dikalov, S.I., Nazarewicz, R.R., Angiotensin II-induced production of mitochondrial reactive oxygen species: potential mechanisms and relevance for cardiovascular disease. Antioxid Redox Signal 19 (2013), 1085–1094.
144. Jaimes, E.A., DeMaster, E.G., Tian, R.X., Raij, L., Stable compounds of cigarette smoke induce endothelial superoxide anion production via NADPH oxidase activation. Arterioscler Thromb Vasc Biol 24 (2004), 1031–1036.
145. Csiszar, A., Podlutsky, A., Wolin, M.S., Losonczy, G., Pacher, P., Ungvari, Z., Oxidative stress and accelerated vascular aging: implications for cigarette smoking. Front Biosci (Landmark Ed) 14 (2009), 3128–3144.
146. Steffen, Y., Vuillaume, G., Stolle, K., et al. Cigarette smoke and LDL cooperate in reducing nitric oxide bioavailability in endothelial cells via effects on both eNOS and NADPH oxidase. Nitric Oxide 27 (2012), 176–184.
147. Heitzer, T., Brockhoff, C., Mayer, B., et al. Tetrahydrobiopterin improves endothelium-dependent vasodilation in chronic smokers: evidence for a dysfunctional nitric oxide synthase. Circ Res 86 (2000), E36–E41.
148. Halliwell, B., The antioxidant paradox: less paradoxical now?. Br J Clin Pharmacol 75 (2013), 637–644.
149. 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. JAMA 297 (2007), 842–857.
150. Biesalski, H.K., Grune, T., Tinz, J., Zöllner, I., Blumberg, J.B., Reexamination of a meta-analysis of the effect of antioxidant supplementation on mortality and health in randomized trials. Nutrients 2 (2010), 929–949.
151. Steinberg, D., Witztum, J.L., Is the oxidative modification hypothesis relevant to human atherosclerosis? Do the antioxidant trials conducted to date refute the hypothesis?. Circulation 105 (2002), 2107–2111.
152. Touyz, R.M., Reactive oxygen species, vascular oxidative stress, and redox signaling in hypertension: what is the clinical significance?. Hypertension 44 (2004), 248–252.
153. Witting, P.K., Upston, J.M., Stocker, R., Role of α-tocopheroxyl radical in the initiation of lipid peroxidation in human low-density lipoprotein exposed to horse radish peroxidase. Biochemistry 36 (1997), 1251–1258.
154. 2 : involvement of α-tocopheroxyl and phosphatidylcholine alkoxyl radicals. Chem Res Toxicol 12 (1999), 1173–1181.
155. Chen, H., Song, Y.S., Chan, P.H., Inhibition of NADPH oxidase is neuroprotective after ischemia-reperfusion. J Cereb Blood Flow Metab 29 (2009), 1262–1272.
156. Jackman, K.A., Miller, A.A., De Silva, T.M., Crack, P.J., Drummond, G.R., Sobey, C.G., Reduction of cerebral infarct volume by apocynin requires pretreatment and is absent in Nox2-deficient mice. Br J Pharmacol 156 (2009), 680–688.
157. Jung, O., Schreiber, J.G., Geiger, H., Pedrazzini, T., Busse, R., Brandes, R.P., gp91phox-containing NADPH oxidase mediates endothelial dysfunction in renovascular hypertension. Circulation 109 (2004), 1795–1801.
158. Kahles, T., Luedike, P., Endres, M., et al. NADPH oxidase plays a central role in blood-brain barrier damage in experimental stroke. Stroke 38 (2007), 3000–3006.
159. Selemidis, S., Sobey, C.G., Wingler, K., Schmidt, H.H., Drummond, G.R., NADPH oxidases in the vasculature: molecular features, roles in disease and pharmacological inhibition. Pharmacol Ther 120 (2008), 254–291.
160. Smith, R.A., Murphy, M.P., Animal and human studies with the mitochondria-targeted antioxidant MitoQ. Ann N Y Acad Sci 1201 (2010), 96–103.
161. 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 24 (2004), 445–450.
162. Brasen, J.H., Leppänen, O., Inkala, M., et al. Extracellular superoxide dismutase accelerates endothelial recovery and inhibits in-stent restenosis in stented atherosclerotic Watanabe heritable hyperlipidemic rabbit aorta. J Am Coll Cardiol 50 (2007), 2249–2253.
163. shc gene expression in human peripheral blood mononuclear cells: relationship to oxidative stress. J Clin Endocrinol Metab 90 (2005), 1130–1136.
164. Venkatasubramanian, S., Noh, R.M., Daga, S., et al. Cardiovascular effects of a novel SIRT1 activator, SRT2104, in otherwise healthy cigarette smokers. J Am Heart Assoc, 2, 2013, e000042.
165. 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 21 (2001), 1249–1259.
166. −/− mice lacking CHOP. Cell Metab 9 (2009), 474–481.
167. Tsukano, H., Gotoh, T., Endo, M., 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 30 (2010), 1925–1932.