NADPH oxidases in heart failure: Poachers or gamekeepers?

Antioxidants and Redox Signaling

Volumn 18, Issue 9, 2013, Pages 1024-1041

  Zhang, Min ^a   Perino, Alessia ^b   Ghigo, Alessandra ^b   Hirsch, Emilio ^b   Shah, Ajay M ^a  

^a KING'S COLLEGE LONDON   (United Kingdom)

^b UNIVERSITY OF TURIN   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ANGIOTENSIN II; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE 1; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE 2; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE 4;

CAPILLARY DENSITY; CELL DEATH; CELL TYPE; CELLULAR DISTRIBUTION; DISEASE COURSE; ENZYME ACTIVITY; FIBROBLAST; FIBROSING ALVEOLITIS; HEART ATRIUM FIBRILLATION; HEART FAILURE; HEART INFARCTION; HEART MUSCLE CELL; HEART MUSCLE FIBROSIS; HEART PROTECTION; HEART VENTRICLE HYPERTROPHY; HUMAN; MOLECULAR MECHANICS; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; REVIEW; SIGNAL TRANSDUCTION; SMOOTH MUSCLE FIBER;

ALDOSTERONE; ANGIOTENSIN II; ANIMALS; APOPTOSIS; ARRHYTHMIAS, CARDIAC; ENZYME ACTIVATION; FIBROBLASTS; FIBROSIS; HEART FAILURE; HUMANS; HYDROGEN PEROXIDE; HYPERTROPHY, LEFT VENTRICULAR; LEUKOCYTES; MEMBRANE GLYCOPROTEINS; MICE; MODELS, CARDIOVASCULAR; MOLECULAR TARGETED THERAPY; MYOCYTES, CARDIAC; NADPH OXIDASE; NEOVASCULARIZATION, PATHOLOGIC; OXIDATIVE STRESS; PROTEIN ISOFORMS; REACTIVE OXYGEN SPECIES; SUBCELLULAR FRACTIONS;

EID: 84874081484     PISSN: 15230864     EISSN: 15577716     Source Type: Journal    
DOI: 10.1089/ars.2012.4550     Document Type: Review

References (220)

1. Abo A, Pick E, Hall A, Totty N, Teahan CG, and Segal AW. Activation of the NADPH oxidase involves the small GTP-binding protein p21rac1. Nature 353: 668-670, 1991.
2. Adam O, Frost G, Custodis F, Sussman MA, Schäfers HJ, Böhm M, and Laufs U. Role of Rac1 GTPase activation in atrial fibrillation. J Am Coll Cardiol 50: 359-367, 2007.
3. Ago T, Kitazono T, Ooboshi H, Iyama T, Han YH, Takada J, Wakisaka M, Ibayashi S, Utsumi H, and Iida M. Nox4 as the major catalytic component of an endothelial NAD(P)H oxidase. Circulation 109: 227-233, 2004.
4. Ago T, Kuroda J, Pain J, Fu C, Li H, and Sadoshima J. Upregulation of Nox4 by hypertrophic stimuli promotes apoptosis and mitochondrial dysfunction in cardiac myo-cytes. Circ Res 106: 1253-1264, 2010.
5. Aguirre JS and Lambeth JD. Nox enzymes from fungus to fly to fish and what they tell us about Nox function in mammals. Free Radic Biol Med 49: 1342-1353, 2010.
6. Akki A, Zhang M, Murdoch C, Brewer A, and Shah AM. NADPH oxidase signaling and cardiac myocyte function. J Mol Cell Cardiol 47: 15-22, 2009.
7. Amar D, Zhang H, Heerdt PM, Park B, Fleisher M, and Thaler HT. Statin use is associated with a reduction in atrial fibrillation after noncardiac thoracic surgery independent of C-reactive protein. Chest 128: 3421-3427, 2005.
8. Anilkumar N, Sirker A, and Shah AM. Redox sensitive signaling pathways in cardiac remodeling, hypertrophy and failure. Front Biosci 14: 3168-3187, 2009.
9. Anilkumar N, Weber R, Zhang M, Brewer A, and Shah AM. Nox4 and nox2 NADPH oxidases mediate distinct cellular redox signaling responses to agonist stimulation. Arterioscler Thromb Vasc Biol 28: 1347-1354, 2008.
10. Aon MA, Cortassa S, and O'Rourke B. Redox-optimized ROS balance: A unifying hypothesis. Biochim Biophys Acta 1797: 865-877, 2010.
11. Awad AE, Kandalam V, Chakrabarti S, Wang X, Penninger JM, Davidge ST, Oudit GY, and Kassiri Z. Tumor necrosis factor induces matrix metalloproteinases in cardiomyocytes and cardiofibroblasts differentially via superoxide production in a PI3Kc-dependent manner. Am J Physiol Cell Physiol 298: C679-C692, 2010.
12. Babior BM. NADPH oxidase: an update. Blood 93: 1464-1476, 1999.
13. Balteau M, Tajeddine N, de Meester C, Ginion A, Des Ro-siers C, Brady NR, Sommereyns C, Horman S, Vano-verschelde JL, Gailly P, Hue L, Bertrand L, and Beauloye C. NADPH oxidase activation by hyperglycaemia in cardio-myocytes is independent of glucose metabolism but requires SGLT1. Cardiovasc Res 92: 237-246, 2011.
14. Basuroy S, Tcheranova D, Bhattacharya S, Leffler CW, and Parfenova H. Nox4 NADPH oxidase-derived reactive oxygen species, via endogenous carbon monoxide, promote survival of brain endothelial cells during TNF-a-induced apoptosis. Am J Physiol Cell Physiol 300: C256-C265, 2011.
15. Bauersachs J, Galuppo P, Fraccarollo D, Christ M, and Ertl G. Improvement of left ventricular remodeling and function by hydroxymethylglutaryl coenzyme a reductase inhibition with cerivastatin in rats with heart failure after myocardial infarction. Circulation 104: 982-985, 2001.
16. Bauldry SA, Nasrallah VN, and Bass DA. Activation of NADPH oxidase in human neutrophils permeabilized with Staphylococcus aureus alpha-toxin. A lower Km when the enzyme is activated in situ. J Biol Chem 267: 323-330, 1992.
17. Bedard K and Krause KH. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysi-ology. Physiol Rev 87: 245-313, 2007.
18. Bell RM, Cave AC, Johar S, Hearse DJ, Shah AM, and Shattock MJ. Pivotal role of NOX-2-containing NADPH oxidase in early ischemic preconditioning. FASEB J 19: 2037-2039, 2005.
19. Bendall JK, Cave AC, Heymes C, Gall N, and Shah AM. Pivotal role of a gp91(phox)-containing NADPH oxidase in angiotensin II-induced cardiac hypertrophy in mice. Circulation 105: 293-296, 2002.
20. Bendall JK, Rinze R, Adlam D, Tatham AL, de Bono J, and Channon KM. Endothelial Nox2 overexpression potentiates vascular oxidative stress and hemodynamic response to angiotensin II. Circ Res 100: 1016-1025, 2007.
21. Borchi E, Bargelli V, Stillitano F, Giordano C, Sebastiani M, Nassi PA, d'Amati G, Cerbai E, and Nediani C. Enhanced ROS production by NADPH oxidase is correlated to changes in antioxidant enzyme activity in human heart failure. Biochim Biophys Acta 1802: 331-338, 2010.
22. Boudina S and Abel ED. Diabetic cardiomyopathy revisited. Circulation 115: 3213-3223, 2007.
23. Brandes RP, Weissmann N, and Schröder K. NADPH oxi-dases in cardiovascular disease. Free Radic Biol Med 49: 687-706, 2010.
24. Bravo Jn, Karathanassis D, Pacold CM, Pacold ME, Ellson CD, Anderson KE, Butler PJ, Lavenir I, Perisic O, Hawkins PT, Stephens L, and Williams RL. The crystal structure of the PX domain from p40phox bound to phosphatidylino-sitol 3-phosphate. Mol Cell 8: 829-839, 2001.
25. Brewer AC, Murray TVA, Arno M, Zhang M, Anilkumar NP, Mann GE, and Shah AM. Nox4 regulates Nrf2 and glutathione redox in cardiomyocytes in vivo. Free Radic Biol Med 51: 205-215, 2011.
26. Brown DI and Griendling KK. Nox proteins in signal transduction. Free Radic Biol Med 47: 1239-1253, 2009.
27. Buul JDV, Fernandez-Borja M, Anthony EC, and Hordijk PL. Expression and localization of NOX2 and NOX4 in primary human endothelial cells. Antioxid Redox Signal 7: 308-317, 2005.
28. Byrne JA, Grieve DJ, Bendall JK, Li JM, Gove C, Lambeth JD, Cave AC, and Shah AM. Contrasting roles of NADPH oxidase isoforms in pressure-overload versus angiotensin II-induced cardiac hypertrophy. Circ Res 93: 802-805, 2003.
29. Cai H, Davis ME, Drummond GR, and Harrison DG. Induction of endothelial NO synthase by hydrogen peroxide via a Ca2+/calmodulin-dependent protein kinase II/janus kinase 2-dependent pathway. Arterioscler Thromb Vasc Biol 21: 1571-1576, 2001.
30. Carnes CA, Chung MK, Nakayama T, Nakayama H, Baliga RS, Piao S, Kanderian A, Pavia S, Hamlin RL, McCarthy PM, Bauer JA, and Van Wagoner DR. Ascorbate attenuates atrial pacing-induced peroxynitrite formation and electrical remodeling and decreases the incidence of postoperative atrial fibrillation. Circ Res 89: e32-e38, 2001.
31. Cave AC, Brewer AC, Narayanapanicker A, Ray R, Grieve DJ, Walker S, and Shah AM. NADPH oxidases in cardiovascular health and disease. Antioxid Redox Signal 8: 691-728, 2006.
32. Chen K, Kirber MT, Xiao H, Yang Y, and Keaney JF. Regulation of ROS signal transduction by NADPH oxidase 4 localization. J Cell Biol 181: 1129-1139, 2008.
33. Cherednichenko G, Zima AV, Feng W, Schaefer S, Blatter LA, and Pessah IN. NADH oxidase activity of rat cardiac sarcoplasmic reticulum regulates calcium-induced calcium release. Circ Res 94: 478-486, 2004.
34. Clempus RE, Sorescu D, Dikalova AE, Pounkova L, Jo P, Sorescu GP, Lassegue B, and Griendling KK. Nox4 is required for maintenance of the differentiated vascular smooth muscle cell phenotype. Arterioscler Thromb Vasc Biol 27: 42-48, 2007.
35. Cook NR, Albert CM, Gaziano JM, Zaharris E, MacFadyen J, Danielson E, Buring JE, and Manson JE. A randomized factorial trial of vitamins C and E and beta carotene in the secondary prevention of cardiovascular events in women: results from the Women's Antioxidant Cardiovascular Study. Arch Intern Med 167: 1610-1618, 2007.
36. Craige SM, Chen K, Pei Y, Li C, Huang X, Chen, C, Shibata R, Sato K, Walsh K, and Keaney JF. NADPH oxidase 4 promotes endothelial angiogenesis through endothelial nitric oxide synthase activation/clinical perspective. Circulation 124: 731-740, 2011.
37. Cross AR, Parkinson JF, and Jones OT. The superoxide-generating oxidase of leucocytes. NADPH-dependent reduction of flavin and cytochrome b in solubilized preparations. Biochem J 223: 337-344, 1984.
38. Csányi G, Taylor WR, and Pagano PJ. NOX and inflammation in the vascular adventitia. Free Radic Biol Med 47: 1254-1266, 2009.
39. Cucoranu I, Clempus R, Dikalova A, Phelan PJ, Ariyan S, Dikalov S, and Sorescu D. NAD(P)H oxidase 4 mediates transforming growth factor-{beta}1-Induced differentiation of cardiac fibroblasts into myofibroblasts. Circ Res 97: 900-907, 2005.
40. Damilano F, Franco I, Perrino C, Schaefer K, Azzolino O, Carnevale D, Cifelli G, Carullo P, Ragona R, Ghigo A, Perino A, Lembo G, and Hirsch E. Distinct effects of leukocyte and cardiac phosphoinositide 3-kinase c activity in pressure overload-induced cardiac failure/clinical perspective. Circulation 123: 391-399, 2011.
41. Datla SR, Peshavariya H, Dusting GJ, Mahadev K, Goldstein BJ, and Jiang F. Important role of Nox4 type NADPH oxidase in angiogenic responses in human microvascular endothelial cells in vitro. Arterioscler Thromb Vasc Biol 27: 2319-2324, 2007.
42. Diaz B, Shani G, Pass I, Anderson D, Quintavalle M, and Courtneidge SA. Tks5-dependent, Nox-mediated generation of reactive oxygen species is necessary for invadopodia formation. Sci Signal 2: ra53, 2009.
43. Diekmann D, Abo A, Johnston C, Segal AW, and Hall A. Interaction of Rac with p67phox and regulation of phagocytic NADPH oxidase activity. Science 265: 531-533, 1994.
44. Dikalov SI, Dikalova AE, Bikineyeva AT, Schmidt HH, Harrison DG, and Griendling KK. Distinct roles of Nox1 and Nox4 in basal and angiotensin II-stimulated superox-ide and hydrogen peroxide production. Free Radic Biol Med 45: 1340-1351, 2008.
45. Dinauer MC and Orkin SH. Chronic granulomatous disease. Annu Rev Med 43: 117-124, 1992.
46. Doerries C, Grote K, Hilfiker-Kleiner D, Luchtefeld M, Schaefer A, Holland SM, Sorrentino S, Manes C, Schieffer B, Drexler H, and Landmesser U. Critical role of the NAD(P)H oxidase subunit p47phox for left ventricular remodeling/dysfunction and survival after myocardial infarction. Circ Res 100: 894-903, 2007.
47. Donoso P, Sanchez G, Bull R, and Hidalgo C. Modulation of cardiac ryanodine receptor activity by ROS and RNS. Front Biosci 16: 553-567, 2011.
48. Doughan AK, Harrison DG, and Dikalov SI. Molecular mechanisms of angiotensin II-mediated mitochondrial dysfunction. Circ Res 102: 488-496, 2008.
49. Drummond GR, Selemidis S, Griendling KK, and Sobey CG. Combating oxidative stress in vascular disease: NADPH oxidases as therapeutic targets. Nat Rev Drug Discov 10: 453-471, 2011.
50. Dudley SC, Hoch NE, McCann LA, Honeycutt C, Diamandopoulos L, Fukai T, Harrison DG, Dikalov SI, and Langberg J. Atrial fibrillation increases production of superoxide by the left atrium and left atrial appendage. Circulation 112: 1266-1273, 2005.
51. Edderkaoui M, Nitsche C, Zheng L, Pandol SJ, Gukovsky I, and Gukovskaya AS. NADPH oxidase activation in pancreatic cancer cells is mediated through Akt-dependent up-regulation of p22phox. J Biol Chem 286: 7779-7787, 2011.
52. Ehrlich JR, Hohnloser SH, and Nattel S. Role of angiotensin system and effects of its inhibition in atrial fibrillation: clinical and experimental evidence. Eur Heart J 27: 512-518, 2006.
53. Ellmark SHM, Dusting GJ, Ng Tang Fui M, Guzzo-Pernell N, and Drummond GR. The contribution of Nox4 to NADPH oxidase activity in mouse vascular smooth muscle. Cardiovasc Res 65: 495-504, 2005.
54. Ellson C, Davidson K, Anderson K, Stephens LR, and Hawkins PT. PtdIns3P binding to the PX domain of p40phox is a physiological signal in NADPH oxidase activation. EMBO J 25: 4468-4478, 2006.
55. Ellson CD, Gobert-Gosse S, Anderson KE, Davidson K, Erdjument-Bromage H, Tempst P, Thuring JW, Cooper MA, Lim ZY, Holmes AB, Gaffney PRJ, Coadwell J, Chil-vers ER, Hawkins PT, and Stephens LR. PtdIns(3)P regulates the neutrophil oxidase complex by binding to the PX domain of p40phox. Nat Cell Biol 3: 679-682, 2001.
56. Erickson JR, He BJ, Grumbach IM, and Anderson ME. CaMKII in the cardiovascular system: sensing redox states. Physiol Rev 91: 889-915, 2011.
57. Erickson JR, Joiner Ml, Guan X, Kutschke W, Yang J, Oddis CV, Bartlett RK, Lowe JS, O'Donnell SE, Aykin-Burns N, Zimmerman MC, Zimmerman K, Ham AJ, Weiss RM, Spitz DR, Shea MA, Colbran RJ, Mohler PJ, and Anderson ME. ADynamic pathway for calcium-independent activation of CaMKII by methionine oxidation. Cell 133: 462-474, 2008.
58. Ewer MS and Ewer SM. Cardiotoxicity of anticancer treatments: what the cardiologist needs to know. Nat Rev Cardiol 7: 564-575, 2010.
59. Faust LR, el Benna J, Babior BM, and Chanock SJ. The phosphorylation targets of p47phox, a subunit of the respiratory burst oxidase. Functions of the individual target serines as evaluated by site-directed mutagenesis. J Clin Invest 96: 1499-1505, 1995.
60. Filomeni G and Ciriolo MR. Redox control of apoptosis: an update. Antioxid Redox Signal 8: 2187-2192, 2006.
61. Foo RS, Mani K, and Kitsis RN. Death begets failure in the heart. J Clin Invest 115: 565-571, 2005.
62. Fraccarollo D, Berger S, Galuppo P, Kneitz S, Hein L, Schütz G, Frantz S, Ertl G, and Bauersachs J. Deletion of cardiomyocyte mineralocorticoid receptor ameliorates adverse remodeling after myocardial infarction/clinical perspective. Circulation 123: 400-408, 2011.
63. Frangogiannis NG, Ren G, Dewald O, Zymek P, Haudek S, Koerting A, Winkelmann K, Michael LH, Lawler J, and Entman ML. Critical role of endogenous thrombospondin-1 in preventing expansion of healing myocardial infarcts. Circulation 111: 2935-2942, 2005.
64. Fukui T, Yoshiyama M, Hanatani A, Omura T, Yoshikawa J, and Abe Y. Expression of p22-phox and gp91-phox, essential components of NADPH oxidase, increases after myocardial infarction. Biochem Biophys Res Commun 281: 1200-1206, 2001.
65. Geiszt M. NADPH oxidases: new kids on the block. Cardiovasc Res 71: 289-299, 2006.
66. Gerald D, Berra E, Frapart YM, Chan DA, Giaccia AJ, Mansuy D, Pouysségur J, Yaniv M, and Mechta-Grigoriou F. JunD reduces tumor angiogenesis by protecting cells from oxidative stress. Cell 118: 781-794, 2004.
67. Gilleron Mn, Marechal X, Montaigne D, Franczak J, Ne-viere R, and Lancel S. NADPH oxidases participate to doxorubicin-induced cardiac myocyte apoptosis. Biochem and Biophys Res Commun 388: 727-731, 2009.
68. Giordano FJ. Oxygen, oxidative stress, hypoxia, and heart failure. J Clin Invest 115: 500-508, 2005.
69. Gorzalczany Y, Sigal N, Itan M, Lotan O, and Pick E. Targeting of Rac1 to the phagocyte membrane is sufficient for the induction of NADPH oxidase assembly. J Biol Chem 275: 40073-40081, 2000.
70. Greer SN, Metcalf JL, Wang Y, and Ohh M. The updated biology of hypoxia-inducible factor. EMBO J 31: 2448-2460, 2012.
71. Griendling KK, Minieri CA, Ollerenshaw JD, and Alexander RW. Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells. Circ Res 74: 1141-1148, 1994.
72. Griendling KK, Sorescu D, and Ushio-Fukai M. NAD(P)H Oxidase: role in cardiovascular biology and disease. Circ Res 86: 494-501, 2000.
73. Grieve DJ, Byrne JA, Siva A, Layland J, Johar S, Cave AC, and Shah AM. Involvement of the nicotinamide adenosine dinucleotide phosphate oxidase isoform Nox2 in cardiac contractile dysfunction occurring in response to pressure overload. J Am Coll Cardiol 47: 817-826, 2006.
74. Grishko V, Pastukh V, Solodushko V, Gillespie M, Azuma J, and Schaffer S. Apoptotic cascade initiated by angioten-sin II in neonatal cardiomyocytes: role of DNA damage. Am J Physiol Heart Circ Physiol 285: H2364-H2372, 2003.
75. Groemping Y, Lapouge K, Smerdon SJ, and Rittinger K. Molecular basis of phosphorylation-induced activation of the NADPH oxidase. Cell 113: 343-355, 2003.
76. Grote K, Flach I, Luchtefeld M, Akin E, Holland SM, Drexler H, and Schieffer B. Mechanical stretch enhances mRNA expression and proenzyme release of matrix me-talloproteinase-2 (MMP-2) via NAD(P)H oxidase-derived reactive oxygen species. Circ Res 92: e80-e86, 2003.
77. Gunja-Smith Z, Morales AR, Romanelli R, and Woessner JF, Jr. Remodeling of human myocardial collagen in idio-pathic dilated cardiomyopathy. Role of metalloproteinases and pyridinoline cross-links. Am J Pathol 148: 1639-1648, 1996.
78. Gupte SA, Levine RJ, Gupte RS, Young ME, Lionetti V, Labinskyy V, Floyd BC, Ojaimi C, Bellomo M, Wolin MS, and Recchia FA. Glucose-6-phosphate dehydrogenase-derived NADPH fuels superoxide production in the failing heart. J Mol Cell Cardiol 41: 340-349, 2006.
79. Halestrap AP. What is the mitochondrial permeability transition pore? J Mol Cell Cardiol 46: 821-831, 2009.
80. Häuselmann SpP, Rosc-Schlüter BI, Lorenz V, Plaisance I, Brink M, Pfister O, and Kuster GM. b1-Integrin is up-regulated via Rac1-dependent reactive oxygen species as part of the hypertrophic cardiomyocyte response. Free Radic Biol Med 51: 609-618, 2011.
81. Hawkins PT, Davidson K, and Stephens LR. The role of PI3Ks in the regulation of the neutrophil NADPH oxidase. Biochem Soc Symp 74: 59-67, 2007.
82. Hayashi H, Kobara M, Abe M, Tanaka N, Gouda E, Toba H, Yamada H, Tatsumi T, Nakata T, and Matsubara H. Aldosterone nongenomically produces NADPH oxidase-dependent reactive oxygen species and induces myocyte apoptosis. Hypertens Res 31: 363-375, 2008.
83. Hayashidani S, Tsutsui H, Shiomi T, Suematsu N, Kinugawa S, Ide T, Wen J, and Takeshita A. Fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, attenuates left ventricular remodeling and failure after experimental myocardial infarction. Circulation 105: 868-873, 2002.
84. He BJ, Joiner Ml, Singh MV, Luczak ED, Swaminathan PD, Koval OM, Kutschke W, Allamargot C, Yang J, Guan X, Zimmerman K, Grumbach IM, Weiss RM, Spitz DR, Sigmund CD, Blankesteijn WM, Heymans S, Mohler PJ, and Anderson ME. Oxidation of CaMKII determines the cardiotoxic effects of aldosterone. Nat Med 17: 1610-1618, 2011.
85. Healey JS, Baranchuk A, Crystal E, Morillo CA, Garfinkle M, Yusuf S, and Connolly SJ. Prevention of atrial fibrillation with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: a meta-analysis. J Am Coll Cardiol 45: 1832-1839, 2005.
86. Heusch P, Canton M, Aker S, van de Sand A, Konietzka I, Rassaf T, Menazza S, Brodde OE, Di Lisa F, Heusch G, and Schulz R. The contribution of reactive oxygen species and p38 mitogen-activated protein kinase to myofilament oxidation and progression of heart failure in rabbits. Br J Pharmacol 160: 1408-1416, 2010.
87. Heymans S, Luttun A, Nuyens D, Theilmeier G, Creemers E, Moons L, Dyspersin GD, Cleutjens JP, Shipley M, Angellilo A, Levi M, Nube O, Baker A, Keshet E, Lupu F, Herbert JM, Smits JF, Shapiro SD, Baes M, Borgers M, Collen D, Daemen MJ, and Carmeliet P. Inhibition of plasminogen activators or matrix metalloproteinases prevents cardiac rupture but impairs therapeutic angiogenesis and causes cardiac failure. Nat Med 5: 1135-1142, 1999.
88. Heymes C, Bendall JK, Ratajczak P, Cave AC, Samuel JL, Hasenfuss G, and Shah AM. Increased myocardial NADPH oxidase activity in human heart failure. J Am Coll Cardiol 41: 2164-2171, 2003.
89. Hilenski LL, Clempus RE, Quinn MT, Lambeth JD, and Griendling KK. Distinct subcellular localizations of Nox1 and Nox4 in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 24: 677-683, 2004.
90. Hingtgen SD, Tian X, Yang J, Dunlay SM, Peek AS, Wu Y, Sharma RV, Engelhardt JF, and Davisson RL. Nox2-containing NADPH oxidase and Akt activation play a key role in angiotensin II-induced cardiomyocyte hypertrophy. Physiol Genomics 26: 180-191, 2006.
91. Hirotani S, Otsu K, Nishida K, Higuchi Y, Morita T, Na-kayama H, Yamaguchi O, Mano T, Matsumura Y, Ueno H, Tada M, and Hori M. Involvement of nuclear factor-{kappa}B and apoptosis signal-regulating kinase 1 in G-protein-coupled receptor agonist-induced cardiomyocyte hypertrophy. Circulation 105: 509-515, 2002.
92. Hirsch E, Katanaev VL, Garlanda C, Azzolino O, Pirola L, Silengo L, Sozzani S, Mantovani A, Altruda F, and Wy-mann MP. Central role for G protein-coupled phosphoi-nositide 3-kinase gamma in inflammation. Science 287: 1049-1053, 2000.
93. Hoffmeyer MR, Jones SP, Ross CR, Sharp B, Grisham MB, Laroux FS, Stalker TJ, Scalia R, and Lefer DJ. Myocardial ischemia/reperfusion injury in NADPH oxidase-deficient mice. Circ Res 87: 812-817, 2000.
94. Hu C, Chen J, Dandapat A, Fujita Y, Inoue N, Kawase Y, Jishage K, Suzuki H, Li D, Hermonat PL, Sawamura T, and Mehta JL. LOX-1 abrogation reduces myocardial ischemia-reperfusion injury in mice. J Mol Cell Cardiol 44: 76-83, 2008.
95. Ide T, Tsutsui H, Kinugawa S, Suematsu N, Hayashidani S, Ichikawa K, Utsumi H, Machida Y, Egashira K, and Take-shita A. Direct evidence for increased hydroxyl radicals originating from superoxide in the failing myocardium. Circ Res 86: 152-157, 2000.
96. Infanger DW, Cao X, Butler SD, Burmeister MA, Zhou Y, Stupinski JA, Sharma RV, and Davisson RL. Silencing Nox4 in the paraventricular nucleus Improves myocardial infarction-induced cardiac dysfunction by attenuating sym-pathoexcitation and periinfarct apoptosis. Circ Res 106: 1763-1774, 2010.
97. Izumiya Y, Kim S, Izumi Y, Yoshida K, Yoshiyama M, Matsuzawa A, Ichijo H, and Iwao H. Apoptosis signal-regulating kinase 1 plays a pivotal role in angiotensin II-induced cardiac hypertrophy and remodeling. Circ Res 93: 874-883, 2003.
98. Janicki JS, Brower GL, Gardner JD, Chancey AL, and Stewart JA. The dynamic interaction between matrix me-talloproteinase activity and adverse myocardial remodeling. Heart Fail Rev 9: 33-42, 2004.
99. Jaquet V, Scapozza L, Clark RA, Krause KH, and Lambeth JD. Small-molecule NOX inhibitors: ROS-generating NADPH oxidases as therapeutic targets. Antioxid Redox Signal 11: 2535-2552, 2009.
100. Johar S, Cave AC, Narayanapanicker A, Grieve DJ, and Shah AM. Aldosterone mediates angiotensin II-induced interstitial cardiac fibrosis via a Nox2-containing NADPH oxidase. FASEB J 20: 1546-1548, 2006.
101. Kaludercic N, Carpi A, Menabò R, Di Lisa F, and Paolocci N. Monoamine oxidases (MAO) in the pathogenesis of heart failure and ischemia/reperfusion injury. Biochim Biophys Acta 1813: 1323-1332, 2011.
102. Kanai F, Liu H, Field SJ, Akbary H, Matsuo T, Brown GE, Cantley LC, and Yaffe MB. The PX domains of p47phox and p40phox bind to lipid products of PI(3)K. Nat Cell Biol 3: 675-678, 2001.
103. Kang YJ, Chen Y, and Epstein PN. Suppression of doxo-rubicin cardiotoxicity by overexpression of catalase in the heart of transgenic mice. J Biol Chem 271: 12610-12616, 1996.
104. Karathanassis D, Stahelin RV, Bravo J, Perisic O, Pacold CM, Cho W, and Williams RL. Binding of the PX domain of p47(phox) to phosphatidylinositol 3, 4-bisphosphate and phosphatidic acid is masked by an intramolecular interaction. EMBO J 21: 5057-5068, 2002.
105. Kim C, Marchal CC, Penninger J, and Dinauer MC. The hemopoietic Rho/Rac guanine nucleotide exchange factor Vav1 regulates N-formyl-methionyl-leucyl- phenylalanine-activated neutrophil functions. J Immunol 171: 4425-4430, 2003.
106. Kim YM, Guzik TJ, Zhang YH, Zhang MH, Kattach H, Ratnatunga C, Pillai R, Channon KM, and Casadei B. A myocardial Nox2 containing NAD(P)H oxidase contributes to oxidative stress in human atrial fibrillation. Circ Res 97: 629-636, 2005.
107. Kim YM, Kattach H, Ratnatunga C, Pillai R, Channon KM, and Casadei B. Association of atrial nicotinamide adenine dinucleotide phosphate oxidase activity with the development of atrial fibrillation after cardiac surgery. J Am Coll Cardiol 51: 68-74, 2001.
108. Kimura S, Zhang GX, Nishiyama A, Shokoji T, Yao L, Fan YY, Rahman M, Suzuki T, Maeta H, and Abe Y. Role of NAD(P)H oxidase-and mitochondria-derived reactive oxygen species in cardioprotection of ischemic reperfusion injury by angiotensin II. Hypertension 45: 860-866, 2005.
109. Kinugawa S, Tsutsui H, Hayashidani S, Ide T, Suematsu N, Satoh S, Utsumi H, and Takeshita A. Treatment with di-methylthiourea prevents left ventricular remodeling and failure after experimental myocardial infarction in mice: role of oxidative stress. Circ Res 87: 392-398, 2000.
110. Knaus UG, Heyworth PG, Evans T, Curnutte JT, and Bo-koch GM. Regulation of phagocyte oxygen radical production by the GTP-binding protein Rac 2. Science 254: 1512-1515, 1991.
111. Krijnen PAJ, Meischl C, Hack CE, Meijer CJLM, Visser CA, Roos D, and Niessen HWM. Increased Nox2 expression in human cardiomyocytes after acute myocardial infarction. J Clin Pathol 56: 194-199, 2003.
112. Kuhns DB, Alvord WG, Heller T, Feld JJ, Pike KM, Mar-ciano BE, Uzel G, DeRavin SS, Priel DAL, Soule BP, Zar-ember KA, Malech HL, Holland SM, and Gallin JI. Residual NADPH oxidase and survival in chronic granulomatous disease. N Engl J Med 363: 2600-2610, 2010.
113. Kuroda J, Ago T, Matsushima S, Zhai P, Schneider MD, and Sadoshima J. NADPH oxidase 4 (Nox4) is a major source of oxidative stress in the failing heart. PNAS 107: 15565-15570, 2010.
114. Kuroda J, Nakagawa K, Yamasaki T, Nakamura Ki, Takeya R, Kuribayashi F, Imajoh-Ohmi S, Igarashi K, Shibata Y, Sueishi K, and Sumimoto H. The superoxide-producing NAD(P)H oxidase Nox4 in the nucleus of human vascular endothelial cells. Genes Cells 10: 1139-1151, 2005.
115. Kuster GM, Pimentel DR, Adachi T, Ido Y, Brenner DA, Cohen RA, Liao R, Siwik DA, and Colucci WS. {alpha}-Adrenergic receptor-stimulated hypertrophy in adult rat ventricular myocytes is mediated via thioredoxin-1-sensitive oxidative modification of thiols on Ras. Circulation 111: 1192-1198, 2005.
116. Kuwahara F, Kai H, Tokuda K, Takeya M, Takeshita A, Egashira K, and Imaizumi T. Hypertensive myocardial fi-brosis and diastolic dysfunction. Hypertension 43: 739-745, 2004.
117. Lambeth JD. Nox enzymes and the biology of reactive oxygen. Nat Rev Immunol 4: 181-189, 2004.
118. Lassègue B and Clempus RE. Vascular NAD(P)H oxidases: specific features, expression, and regulation. Am J Physiol Regul Integr Comp Physiol 285: R277-R297, 2003.
119. Lassègue B and Griendling KK. NADPH Oxidases: Functions and pathologies in the vasculature. Arterioscler Thromb Vasc Biol 30: 653-661, 2010.
120. Lee JK, Edderkaoui M, Truong P, Ohno I, Jang KT, Berti A, Pandol SJ, and Gukovskaya AS. NADPH oxidase promotes pancreatic cancer cell survival via inhibiting JAK2 de-phosphorylation by tyrosine phosphatases. Gastroenterology 133: 1637-1648, 2007.
121. Leenen FHH. Brain mechanisms contributing to sympathetic hyperactivity and heart failure. Circ Res 101: 221-223, 2007.
122. Li J, Ichikawa T, Villacorta L, Janicki JS, Brower GL, Ya-mamoto M, and Cui T. Nrf2 protects against maladaptive cardiac responses to hemodynamic stress. Arterioscler Thromb Vasc Biol 29: 1843-1850, 2009.
123. Li J, Zhu H, Shen E, Wan L, Arnold JM, and Peng T. Deficiency of Rac1 Blocks NADPH oxidase activation, inhibits endoplasmic reticulum stress, and reduces myocardial remodeling in a mouse model of type 1 diabetes. Diabetes 59: 2033-2042, 2010.
124. Li JM, Gall NP, Grieve DJ, Chen M, and Shah AM. Activation of NADPH oxidase during progression of cardiac hypertrophy to failure. Hypertension 40: 477-484, 2002.
125. Li JM and Shah AM. Endothelial cell superoxide generation: regulation and relevance for cardiovascular patho-physiology. Am J Physiol Regul Integr Comp Physiol 287: R1014-R1030, 2004.
126. Li JM and Shah AM. Intracellular localization and pre-assembly of the NADPH oxidase complex in cultured en-dothelial cells. J Biol Chem 277: 19952-19960, 2002.
127. Li S, Tabar SS, Malec V, Eul BG, Klepetko W, Weissmann N, Grimminger F, Seeger W, Rose F, and Hänze J. NOX4 regulates ROS levels under normoxic and hypoxic conditions, triggers proliferation, and inhibits apoptosis in pulmonary artery adventitial fibroblasts. Antioxid Redox Signal 10: 1687-1698, 2008.
128. 2+-AT-Pase and myosin heavy chain isozyme switch. Diabetologia 49: 1434-1446, 2006.
129. Li Y, Arnold JM, Pampillo M, Babwah AV, and Peng T. Taurine prevents cardiomyocyte death by inhibiting NADPH oxidase-mediated calpain activation. Free Radic Biol Med 46: 51-61, 2009.
130. Li YY, McTiernan CF, and Feldman AM. Interplay of matrix metalloproteinases, tissue inhibitors of metalloprotei-nases and their regulators in cardiac matrix remodeling. Cardiovasc Res 46: 214-224, 2000.
131. Lima B, Lam GKW, Xie L, Diesen DL, Villamizar N, Nie-naber J, Messina E, Bowles D, Kontos CD, Hare JM, Stamler JS, and Rockman HA. Endogenous S-nitrosothiols protect against myocardial injury. PNAS 106: 6297-6302, 2009.
132. Lindley TE, Doobay MF, Sharma RV, and Davisson RL. Superoxide is involved in the central nervous system activation and sympathoexcitation of myocardial infarction-induced heart failure. Circ Res 94: 402-409, 2004.
133. Lipshultz SE, Rifai N, Dalton VM, Levy DE, Silverman LB, Lipsitz SR, Colan SD, Asselin BL, Barr RD, Clavell LA, Hurwitz CA, Moghrabi A, Samson Y, Schorin MA, Gelber RD, and Sallan SE. The effect of dexrazoxane on myocar-dial injury in doxorubicin-treated children with acute lymphoblastic leukemia. N Engl J Med 351: 145-153, 2004.
134. Liu JJ, Li DL, Zhou J, Sun L, Zhao M, Kong SS, Wang YH, Yu XJ, Zhou J, and Zang WJ. Acetylcholine prevents an-giotensin II-induced oxidative stress and apoptosis in H9c2 cells. Apoptosis 16: 94-103, 2011.
135. Liu Y, Huang H, Xia W, Tang Y, Li H, and Huang C. NADPH oxidase inhibition ameliorates cardiac dysfunction in rabbits with heart failure. Mol Cell Biochem 343: 143-153, 2010.
136. Looi YH, Grieve DJ, Siva A, Walker SJ, Anilkumar N, Cave AC, Marber M, Monaghan MJ, and Shah AM. Involvement of Nox2 NADPH oxidase in adverse cardiac remodeling after myocardial infarction. Hypertension 51: 319-325, 2008.
137. Lu J, Mitra S, Wang X, Khaidakov M, and Mehta JL. Oxi-dative stress and lectin-like ox-LDL-receptor LOX-1 in atherogenesis and tumorigenesis. Antioxid Redox Signal 15: 2301-2333, 2011.
138. Lyle AN, Deshpande NN, Taniyama Y, Seidel-Rogol B, Pounkova L, Du P, Papaharalambus C, Lassègue B, and Griendling KK. Poldip2, a novel regulator of Nox4 and cytoskeletal integrity in vascular smooth muscle cells. Circ Res 105: 249-259, 2009.
139. Maack C, Kartes T, Kilter H, Schafers HJ, Nickenig G, Bohm M, and Laufs U. Oxygen free radical release in human failing myocardium is associated with increased activity of Rac1-GTPase and represents a target for statin treatment. Circulation 108: 1567-1574, 2003.
140. Maffei A, Di Pardo A, Carangi R, Carullo P, Poulet R, Gentile MT, Vecchione C, and Lembo G. Nebivolol induces nitric oxide release in the heart through inducible nitric oxide synthase activation. Hypertension 50: 652-656, 2007.
141. Martyn KD, Frederick LM, von Loehneysen K, Dinauer MC, and Knaus UG. Functional analysis of Nox4 reveals unique characteristics compared to other NADPH oxidases. Cell Signal 18: 69-82, 2006.
142. Matsushima S, Kinugawa S, Yokota T, Inoue N, Ohta Y, Hamaguchi S, and Tsutsui H. Increased myocardial NAD(P)H oxidase-derived superoxide causes the exacerbation of postinfarct heart failure in type 2 diabetes. Am J Physiol Heart Circ Physiol 297: H409-H416, 2009.
143. Matsuzawa A and Ichijo H. Stress-responsive protein ki-nases in redox-regulated apoptosis signaling. Antioxid Re-dox Signal 7: 472-481, 2005.
144. Maytin M, Siwik DA, Ito M, Xiao L, Sawyer DB, Liao R, and Colucci WS. Pressure overload-induced myocardial hypertrophy in mice does not require gp91phox. Circulation 109: 1168-1171, 2004.
145. Meischl C, Krijnen P, Sipkens J, Cillessen S, Muńoz I, Okroj M, Ramska M, Muller A, Visser C, Musters R, Simonides W, Hack C, Roos D, and Niessen H. Ischemia induces nuclear NOX2 expression in cardiomyocytes and subsequently activates apoptosis. Apoptosis 11: 913-921, 2006.
146. Mihm MJ, Yu F, Carnes CA, Reiser PJ, McCarthy PM, Van Wagoner DR, and Bauer JA. Impaired myofibrillar energetics and oxidative injury during human atrial fibrillation. Circulation 104: 174-180, 2001.
147. Murdoch C, Alom-Ruiz S, Wang M, Zhang M, Walker S, Yu B, Brewer A, and Shah A. Role of endothelial Nox2 NADPH oxidase in angiotensin II-induced hypertension and vasomotor dysfunction. Basic Res Cardiol 106: 527-538, 2011.
148. Murdoch CE, Brewer A, Zhang M, Vanhoutte D, Heymans S, and Shah AM. Endothelial-specific overexpression of Nox2 enhances angiotensin II-induced cardiac dysfunction and fibrosis. Circulation 118: S314, 2008.
149. Nakagami H, Takemoto M, and Liao JK. NADPH oxidase-derived superoxide anion mediates angiotensin II-induced cardiac hypertrophy. J Mol Cell Cardiol
150. Oakley FD, Abbott D, Li Q, and Engelhardt JF. Signaling components of redox active endosomes: the redoxosomes. Antioxid Redox Signal 11: 1313-1333, 2009.
151. Pacher P, Liaudet L, Bai P, Mabley JG, Kaminski PM, Virág L, Deb A, Szabò E, Ungvári Zn, Wolin MS, Groves JT, and Szabò C. Potent metalloporphyrin peroxynitrite decomposition catalyst protects against the development of doxorubicin-induced cardiac dysfunction. Circulation 107: 896-904, 2003.
152. Pagano PJ, Chanock SJ, Siwik DA, Colucci WS, and Clark JK. Angiotensin II Induces p67phox mRNA expression and NADPH oxidase superoxide generation in rabbit aortic adventitial fibroblasts. Hypertension 32: 331-337, 1998.
153. 2+-calmod-ulin protein kinase II and promotes a death pathway conserved across different species. Circ Res 105: 1204-1212, 2009.
154. Park HS, Chun JN, Jung HY, Choi C, and Bae YS. Role of NADPH oxidase 4 in lipopolysaccharide-induced proin-flammatory responses by human aortic endothelial cells. Cardiovasc Res 72: 447-455, 2006.
155. Patrucco E, Notte A, Barberis L, Selvetella G, Maffei A, Brancaccio M, Marengo S, Russo G, Azzolino O, Rybalkin SD, Silengo L, Altruda F, Wetzker R, Wymann MP, Lembo G, and Hirsch E. PI3Kc modulates the cardiac response to chronic pressure overload by distinct kinase-dependent and-independent effects. Cell 118: 375-387, 2004.
156. Pendyala S, Gorshkova IA, Usatyuk PV, He D, Pennathur A, Lambeth JD, Thannickal VJ, and Natarajan V. Role of Nox4 and Nox2 in hyperoxia-induced reactive oxygen species generation and migration of human lung endothe-lial cells. Antioxid Redox Signal 11: 747-764, 2008.
157. Privratsky JR, Wold LE, Sowers JR, Quinn MT, and Ren J. AT1 blockade prevents glucose-induced cardiac dysfunction in ventricular myocytes. Hypertension 42: 206-212, 2003.
158. Prosser BL, Ward CW, and Lederer WJ. X-ROS signaling: rapid mechano-chemo transduction in heart. Science 333: 1440-1445, 2011.
159. Qin F, Patel R, Yan C, and Liu W. NADPH oxidase is involved in angiotensin II-induced apoptosis in H9C2 cardiac muscle cells: effects of apocynin. Free Radic Biol Med 40: 236-246, 2006.
160. Qin F, Simeone M, and Patel R. Inhibition of NADPH ox-idase reduces myocardial oxidative stress and apoptosis and improves cardiac function in heart failure after myo-cardial infarction. Free Radic Biol Med 43: 271-281, 2007.
161. Ray R, Murdoch CE, Wang M, Santos CX, Zhang M, Alom-Ruiz S, Anilkumar N, Ouattara A, Cave AC, Walker SJ, Grieve DJ, Charles RL, Eaton P, Brewer AC, and Shah AM. Endothelial Nox4 NADPH oxidase enhances vasodilatation and reduces blood pressure in vivo. Arterioscler Thromb Vasc Biol 31: 1368-1376, 2011.
162. Reilly SN, Jayaram R, Nahar K, Antoniades C, Verheule S, Channon KM, Alp NJ, Schotten U, and Casadei B. Atrial sources of reactive oxygen species vary with the duration and substrate of atrial fibrillation/clinical perspective. Circulation 124: 1107-1117, 2011.
163. 2, a necessary evil for cell signaling. Science 312: 1882-1883, 2006.
164. Rhee SG, Woo HA, Kil IS, and Bae SH. Peroxiredoxin functions as a peroxidase and a regulator and sensor of local peroxides. J Biol Chem 287: 4403-4410, 2012.
165. Roe ND, Thomas DP, and Ren J. Inhibition of NADPH oxidase alleviates experimental diabetes-induced myocar-dial contractile dysfunction. Diabetes Obes Metab 13: 465-473, 2011.
166. Rotrosen D, Yeung CL, Leto TL, Malech HL, and Kwong CH. Cytochrome b558: the flavin-binding component of the phagocyte NADPH oxidase. Science 256: 1459-1462, 1992.
167. Ruckle T, Schwarz MK, and Rommel C. PI3K[gamma] inhibition: towards an "aspirin of the 21st century"? Nat Rev Drug Discov 5: 903-918, 2006.
168. Rude MK, Duhaney TA, Kuster GM, Judge S, Heo J, Co-lucci WS, Siwik DA, and Sam F. Aldosterone stimulates matrix metalloproteinases and reactive oxygen species in adult rat ventricular cardiomyocytes. Hypertension 46: 555-561, 2005.
169. Sanchez G, Escobar Ma, Pedrozo Z, Macho P, Domenech Rl, Härtel S, Hidalgo C, and Donoso P. Exercise and tachycardia increase NADPH oxidase and ryanodine re-ceptor-2 activity: possible role in cardioprotection. Cardio-vasc Res 77: 380-386, 2008.
170. Sanchez G, Pedrozo Z, Domenech RLJ, Hidalgo C, and Donoso P. Tachycardia increases NADPH oxidase activity and RyR2 S-glutathionylation in ventricular muscle. J Mol Cell Cardiol 39: 982-991, 2005.
171. Sano M, Minamino T, Toko H, Miyauchi H, Orimo M, Qin Y, Akazawa H, Tateno K, Kayama Y, Harada M, Shimizu I, Asahara T, Hamada H, Tomita S, Molkentin JD, Zou Y, and Komuro I. p53-induced inhibition of Hif-1 causes cardiac dysfunction during pressure overload. Nature 446: 444-448, 2007.
172. Satoh M, Ogita H, Takeshita K, Mukai Y, Kwiatkowski DJ, and Liao JK. Requirement of Rac1 in the development of cardiac hypertrophy. PNAS 103: 7432-7437, 2006.
173. Schröder K, Zhang M, Benkhoff S, Mieth A, Pliquett R, Kosowski J, Kruse C, Luedike P, Michaelis UR, Weissmann N, Dimmeler S, Shah AM, and Brandes RP. Nox4 is a protective reactive oxygen species generating vascular NADPH oxidase/novelty and significance. Circ Res 110: 1217-1225, 2012.
174. Serpillon S, Floyd BC, Gupte RS, George S, Kozicky M, Neito V, Recchia F, Stanley W, Wolin MS, and Gupte SA. Superoxide production by NAD(P)H oxidase and mitochondria is increased in genetically obese and hyperglyce-mic rat heart and aorta before the development of cardiac dysfunction. The role of glucose-6-phosphate dehydroge-nase-derived NADPH. Am J Physiol Heart Circ Physiol 297: H153-H162, 2009.
175. Serrander L, Cartier L, Bedard K, Banfi B, Lardy B, Plastre O, Sienkiewicz A, Forro L, Schlegel W, and Krause KH. NOX4 activity is determined by mRNA levels and reveals a unique pattern of ROS generation. Biochem J 406: 105-114, 2007.
176. Sesso HD, Buring JE, Christen WG, Kurth T, Belanger C, MacFadyen J, Bubes V, Manson JE, Glynn RJ, and Gaziano JM. Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial. JAMA 300: 2123-2133, 2008.
177. Shah AM and Mann DL. In search of new therapeutic targets and strategies for heart failure: recent advances in basic science. Lancet 378: 704-712, 2011.
178. Shanmugam P, Valente AJ, Prabhu SD, Venkatesan B, Yoshida T, Delafontaine P, and Chandrasekar B. Angio-tensin-II type 1 receptor and NOX2 mediate TCF/LEF and CREB dependent WISP1 induction and cardiomyocyte hypertrophy. J Mol Cell Cardiol 50: 928-938, 2011.
179. Shen E, Li Y, Li Y, Shan L, Zhu H, Feng Q, Arnold JM, and Peng T. Rac1 is required for cardiomyocyte apoptosis during hyperglycemia. Diabetes 58: 2386-2395, 2009.
180. Shiojima I, Sato K, Izumiya Y, Schiekofer S, Ito M, Liao R, Colucci WS, and Walsh K. Disruption of coordinated cardiac hypertrophy and angiogenesis contributes to the transition to heart failure. J Clin Invest 115: 2108-2118, 2005.
181. Shiomi T, Tsutsui H, Matsusaka H, Murakami K, Hayashidani S, Ikeuchi M, Wen J, Kubota T, Utsumi H, and Takeshita A. Overexpression of glutathione peroxidase prevents left ventricular remodeling and failure after myo-cardial infarction in mice. Circulation 109: 544-549, 2004.
182. Shiroshita-Takeshita A, Schram G, Lavoie J, and Nattel S. Effect of simvastatin and antioxidant vitamins on atrial fibrillation promotion by atrial-tachycardia remodeling in dogs. Circulation 110: 2313-2319, 2004.
183. Sirker A, Zhang M, and Shah A. NADPH oxidases in cardiovascular disease: insights from in vivo models and clinical studies. Basic Res Cardiol 106: 735-747, 2011.
184. Sorescu D, Weiss D, Lassègue B, Clempus RE, Szocs K, Sorescu GP, Valppu L, Quinn MT, Lambeth JD, Vega JD, Taylor WR, and Griendling KK. Superoxide production and expression of Nox family proteins in human atherosclerosis. Circulation 105: 1429-1435, 2002.
185. Sorrentino SA, Doerries C, Manes C, Speer T, Dessy C, Lobysheva I, Mohmand W, Akbar R, Bahlmann F, Besler C, Schaefer A, Hilfiker-Kleiner D, Lü scher TF, Balligand JL, Drexler H, and Landmesser U. Nebivolol exerts beneficial effects on endothelial function, early endothelial progenitor cells, myocardial neovascularization, and left ventricular dysfunction early after myocardial infarction beyond conventional b1-blockade. J Am Coll Cardiol 57: 601-611, 2011.
186. Sun QA, Hess DT, Nogueira L, Yong S, Bowles DE, Eu J, Laurita KR, Meissner G, and Stamler JS. Oxygen-coupled redox regulation of the skeletal muscle ryanodine receptor-Ca2+ release channel by NADPH oxidase 4. PNAS 108: 16098-16103, 2011.
187. Sun Y. Oxidative stress and cardiac repair/remodeling following infarction. Am J Med Sci 334: 197-205, 2007.
188. Sun Y, Zhang J, Lu L, Chen SS, Quinn MT, and Weber KT. Aldosterone-induced inflammation in the rat heart: role of oxidative stress. Am J Pathol 161: 1773-1781, 2002.
189. Swaminathan PD, Purohit A, Soni S, Voigt N, Singh MV, Glukhov AV, Gao Z, He BJ, Luczak ED, Joiner ML, Kutschke W, Yang J, Donahue JK, Weiss RM, Grumbach IM, Ogawa M, Chen PS, Efimov I, Dobrev D, Mohler PJ, Hund TJ, and Anderson ME. Oxidized CaMKII causes cardiac sinus node dysfunction in mice. J Clin Invest 121: 3277-3288, 2011.
190. Takac I, Schröder K, Zhang L, Lardy B, Anilkumar N, Lambeth JD, Shah AM, Morel F, and Brandes RP. The E-loop is involved in hydrogen peroxide formation by the NADPH oxidase Nox4. J Biol Chem 286: 13304-13313, 2011.
191. Tanaka K, Honda M, and Takabatake T. Redox regulation of MAPK pathways and cardiac hypertrophy in adult rat cardiac myocyte. J Am Coll Cardiol 37: 676-685, 2001.
192. The Heart Outcomes Prevention Evaluation Study Investigators. Vitamin E supplementation and cardiovascular events in high-risk patients. N Engl J Med 342: 154-160, 2000.
193. Toren F. Oxidant signals and oxidative stress. Curr Opin Cell Biol 15: 247-254, 2003.
194. Tsai CT, Wang DL, Chen WP, Hwang JJ, Hsieh CS, Hsu KL, Tseng CD, Lai LP, Tseng YZ, Chiang FT, and Lin JL. An-giotensin II increases expression of a1C subunit of L-type calcium channel through a reactive oxygen species and cAMP response element-binding protein-dependent pathway in HL-1 myocytes. Circ Res 100: 1476-1485, 2007.
195. Tsutsui H, Kinugawa S, and Matsushima S. Mitochondrial oxidative stress and dysfunction in myocardial remodelling. Cardiovasc Res 81: 449-456, 2009.
196. Uhlinger DJ, Taylor KL, and Lambeth JD. p67-phox enhances the binding of p47-phox to the human neutrophil respiratory burst oxidase complex. J Biol Chem 269: 22095-22098, 1994.
197. Ushio-Fukai M. Compartmentalization of redox signaling through NADPH oxidase-derived ROS. Antioxid Redox Signal 11: 1289-1299, 2009.
198. Vallet P, Charnay Y, Steger K, Ogier-Denis E, Kovari E, Herrmann F, Michel JP, and Szanto I. Neuronal expression of the NADPH oxidase NOX4, and its regulation in mouse experimental brain ischemia. Neuroscience 132: 233-238, 2005.
199. Wang M, Zhang J, Walker SJ, Dworakowski R, Lakatta EG, and Shah AM. Involvement of NADPH oxidase in age-associated cardiac remodeling. J Mol Cell Cardiol 48: 765-772, 2010.
200. Watson F, Robinson J, and Edwards SW. Protein kinase C-dependent and-independent activation of the NADPH oxi-dase of human neutrophils. J Biol Chem 266: 7432-7439, 1991.
201. Welch HCE, Coadwell WJ, Ellson CD, Ferguson GJ, Andrews SR, Erdjument-Bromage H, Tempst P, Hawkins PT, and Stephens LR. P-Rex1, a PtdIns(3, 4, 5)P3-and Gb-regulated guanine-nucleotide exchange factor for Rac. Cell 108: 809-821, 2002.
202. Wendt MC, Daiber A, Kleschyov AL, Mülsch A, Sydow K, Schulz E, Chen K, Keaney J, Lassègue B, Walter U, Griendling KK, and Münzel T. Differential effects of diabetes on the expression of the gp91phox homologues nox1 and nox4. Free Radic Biol Med 39: 381-391, 2005.
203. Whaley-Connell A, Govindarajan G, Habibi J, Hayden MR, Cooper SA, Wei Y, Ma L, Qazi M, Link D, Karuparthi PR, Stump C, Ferrario C, and Sowers Jr. Angiotensin II-mediated oxidative stress promotes myocardial tissue remodeling in the transgenic (mRen2) 27 Ren2 rat. Am J Physiol Endocrinol Metab 293: E355-E363, 2007.
204. Wojnowski L, Kulle B, Schirmer M, Schlüter G, Schmidt A, Rosenberger A, Vonhof S, Bickeböller H, Toliat MR, Suk EK, Tzvetkov M, Kruger A, Seifert S, Kloess M, Hahn H, Loeffler M, Nürnberg P, Pfreundschuh M, Trümper L, Brockmöller J, and Hasenfuss G. NAD(P)H oxidase and multidrug resistance protein genetic polymorphisms are associated with doxorubicin-induced cardiotoxicity. Circulation 112: 3754-3762, 2005.
205. Wold LE, Ceylan-Isik AF, Fang CX, Yang X, Li SY, Sree-jayan N, Privratsky JR, and Ren J. Metallothionein alleviates cardiac dysfunction in streptozotocin-induced diabetes: Role of Ca2+ cycling proteins, NADPH oxidase, poly(ADP-Ribose) polymerase and myosin heavy chain isozyme. Free Radic Biol Med 40: 1419-1429, 2006.
206. 2 mediates endoplasmic reticulum signaling through local ras activation. Mol Cell Biol 30: 3553-3568, 2010.
207. Xia C, Meng Q, Liu LZ, Rojanasakul Y, Wang XR, and Jiang BH. Reactive oxygen species regulate angiogenesis and tumor growth through vascular endothelial growth factor. Cancer Res 67: 10823-10830, 2007.
208. Xiao L, Pimentel DR, Wang J, Singh K, Colucci WS, and Sawyer DB. Role of reactive oxygen species and NAD(P)H oxidase in alpha 1-adrenoceptor signaling in adult rat cardiac myocytes. Am J Physiol Cell Physiol 282: C926-C934, 2002.
209. Xu J, Carretero OA, Liao TD, Peng H, Shesely EG, Xu J, Liu TS, Yang JJ, Reudelhuber TL, and Yang XP. Local angio-tensin II aggravates cardiac remodeling in hypertension. Am J Physiol Heart Circ Physiol 299: H1328-H1338, 2010.
210. Yagi S, Akaike M, Aihara Ki, Ishikawa K, Iwase T, Ikeda Y, Soeki T, Yoshida S, Sumitomo-Ueda Y, Matsumoto T, and Sata M. Endothelial nitric oxide synthase-independent protective action of statin against angiotensin II-induced atrial remodeling via reduced oxidant injury. Hypertension 55: 918-923, 2010.
211. Yazdanpanah B, Wiegmann K, Tchikov V, Krut O, Pon-gratz C, Schramm M, Kleinridders A, Wunderlich T, Kashkar H, Utermohlen O, Bruning JC, Schutze S, and Kronke M. Riboflavin kinase couples TNF receptor 1 to NADPH oxidase. Nature 460: 1159-1163, 2009.
212. Zeng Q, Zhou Q, Yao F, O'Rourke ST, and Sun C. En-dothelin-1 regulates cardiac L-type calcium channels via NAD(P)H oxidase-derived superoxide. J Pharmacol Exp Ther 326: 732-738, 2008.
213. Zhang L, Sheppard OR, Shah AM, and Brewer AC. Positive regulation of the NADPH oxidase NOX4 promoter in vascular smooth muscle cells by E2F. Free Radic Biol Med 45: 679-685, 2008.
214. Zhang M, Brewer AC, Schröder K, Santos CXC, Grieve DJ, Wang M, Anilkumar N, Yu B, Dong X, Walker SJ, Brandes RP, and Shah AM. NADPH oxidase-4 mediates protection against chronic load-induced stress in mouse hearts by enhancing angiogenesis. PNAS 107: 18121-18126, 2010.
215. Zhang M, Kho AL, Anilkumar N, Chibber R, Pagano PJ, Shah AM, and Cave AC. Glycated proteins stimulate reactive oxygen species production in cardiac myocytes: involvement of Nox2 (gp91phox)-containing NADPH oxidase. Circulation 113: 1235-1243, 2006.
216. Zhao Y, McLaughlin D, Robinson E, Harvey AP, Hookham MB, Shah AM, McDermott BJ, and Grieve DJ. Nox2 NADPH oxidase promotes pathologic cardiac remodeling associated with doxorubicin chemotherapy. Cancer Res 70: 9287-9297, 2010.
217. Zhao Z, Fefelova N, Shanmugam M, Bishara P, Babu GJ, and Xie LH. Angiotensin II induces afterdepolarizations via reactive oxygen species and calmodulin kinase II signaling. J Mol Cell Cardiol 50: 128-136, 2011.
218. Zhou C, Ziegler C, Birder LA, Stewart AFR, and Levitan ES. Angiotensin II and stretch activate NADPH oxidase to destabilize cardiac Kv4.3 channel mRNA. Circ Res 98: 1040-1047, 2006.
219. Zima AV and Blatter LA. Redox regulation of cardiac calcium channels and transporters. Cardiovasc Res 71: 310-321, 2006.
220. Zorov DB, Filburn CR, Klotz LO, Zweier JL, and Sollott SJ. Reactive oxygen species (Ros-induced) Ros release. J Exp Med 192: 1001-1014, 2000.