ROS regulation of microdomain Ca2+ signalling at the dyads

Cardiovascular Research

Volumn 98, Issue 2, 2013, Pages 248-258

  Zhang, Huiliang ^a   Gomez, Ana M ^b   Wang, Xianhua ^a   Yan, Yuan ^a   Zheng, Ming ^a   Cheng, Heping ^a  

^a PEKING UNIVERSITY   (China)

^b INSERM   (France)

Author keywords

Ca2+ spark; Mitochondria; Reactive oxygen species; Ryanodine receptor; Superoxide flash

Indexed keywords

CALCIUM ION; CALMODULIN; CYCLIC GMP DEPENDENT PROTEIN KINASE; GLUTATHIONE PEROXIDASE; MITOCHONDRIAL PERMEABILITY TRANSITION PORE; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE; RYANODINE RECEPTOR; THIOREDOXIN REDUCTASE;

CELL ADHESION; CELL DAMAGE; CELL MEMBRANE; CELL MEMBRANE DEPOLARIZATION; CELL VOLUME; DISEASE COURSE; ELECTRON TRANSPORT; ENDOPLASMIC RETICULUM; HEART MUSCLE CONTRACTILITY; HEART MUSCLE POTENTIAL; HEART PRELOAD; HEART VENTRICLE HYPERTROPHY; HUMAN; LIPID BILAYER; MEMBRANE DEPOLARIZATION; MITOCHONDRIAL MEMBRANE; MITOCHONDRIAL RESPIRATION; NONHUMAN; OSCILLATION; OXIDATION; OXIDATIVE STRESS; PRIORITY JOURNAL; RESPIRATORY CHAIN; REVIEW; SARCOPLASMIC RETICULUM; SIGNAL TRANSDUCTION; TIGHT JUNCTION; TRANSVERSE TUBULAR SYSTEM;

ANIMALS; CALCIUM SIGNALING; EXCITATION CONTRACTION COUPLING; HUMANS; MEMBRANE MICRODOMAINS; MITOCHONDRIA, HEART; MYOCYTES, CARDIAC; NADPH OXIDASE; REACTIVE OXYGEN SPECIES; SARCOPLASMIC RETICULUM; SUPEROXIDE DISMUTASE;

EID: 84877281175     PISSN: 00086363     EISSN: 17553245     Source Type: Journal    
DOI: 10.1093/cvr/cvt050     Document Type: Review

References (110)

1. Thannickal VJ, Fanburg BL. Reactive oxygen species in cell signaling. Am J Physiol Lung Cell Mol Physiol 2000;279:L1005-L1028.
2. Owusu-Ansah E, Banerjee U. Reactive oxygen species prime Drosophila haematopoietic progenitors for differentiation. Nature 2009;461:537-541.
3. Maryanovich M, Gross A. A ROS rheostat for cell fate regulation. Trends Cell Biol 2013;23:129-134.
4. Adler V, Yin Z, Tew KD, Ronai Z. Role of redox potential and reactive oxygen species in stress signaling. Oncogene 1999;18:6104-6111.
5. Niethammer P, Grabher C, Look AT, Mitchison TJ. A tissue-scale gradient of hydrogen peroxide mediates rapid wound detection in zebrafish. Nature 2009;459: 996-999.
6. Yoo SK, Starnes TW, Deng Q, Huttenlocher A. Lyn is a redox sensor that mediates leukocyte wound attraction in vivo. Nature 2011;480:109-112.
7. Yan Y, Wei CL, Zhang WR, Cheng HP, Liu J. Cross-talk between calcium and reactive oxygen species signaling. Acta Pharmacol Sin 2006;27:821-826.
8. Hidalgo C, Donoso P. Crosstalk between calcium and redox signaling: from molecular mechanisms to health implications. Antioxid Redox Signal 2008;10:1275-1312.
9. Soeller C, Cannell MB. Examination of the transverse tubular system in living cardiac rat myocytes by 2-photon microscopy and digital image-processing techniques. Circ Res 1999;84:266-275.
10. Song LS, Guatimosim S, Gomez-Viquez L, Sobie EA, Ziman A, Hartmann H et al. Calcium biology of the transverse tubules in heart. Ann N Y Acad Sci 2005;1047: 99-111.
11. Cheng H, Cannell MB, Lederer WJ. Propagation of excitation-contraction coupling into ventricular myocytes. Pflugers Arch 1994;428:415-417.
12. Cheng H, Lederer WJ, Cannell MB. Calcium sparks: elementary events underlying excitation-contraction coupling in heart muscle. Science 1993;262:740-744.
13. Cheng H, Lederer WJ. Calcium sparks. Physiol Rev 2008;88:1491-1545.
14. Stern MD. Theory of excitation-contraction coupling in cardiac muscle. Biophys J 1992;63:497-517.
15. Ramesh V, Sharma VK, Sheu SS, Franzini-Armstrong C. Structural proximity of mitochondria to calcium release units in rat ventricular myocardium may suggest a role in Ca2+ sequestration. Ann N Y Acad Sci 1998;853:341-344.
16. Csordas G, Renken C, Varnai P, Walter L, Weaver D, Buttle KF et al. Structural and functional features and significance of the physical linkage between ER and mitochondria. J Cell Biol 2006;174:915-921.
17. Garcia-Perez C, Hajnoczky G, Csordas G. Physical coupling supports the local Ca2+ transfer between sarcoplasmic reticulum subdomains and the mitochondria in heart muscle. J Biol Chem 2008;283:32771-32780.
18. Garcia-Perez C, Schneider TG, Hajnoczky G, Csordas G. Alignment of sarcoplasmic reticulum-mitochondrial junctions with mitochondrial contact points. Am J Physiol Heart Circ Physiol 2011;301:H1907-H1915.
19. Wang SQ, Song LS, Lakatta EG, Cheng H. Ca2+ signalling between single L-type Ca2+ channels and ryanodine receptors in heart cells. Nature 2001;410:592-596.
20. Brochet DX, Yang D, Di Maio A, Lederer WJ, Franzini-Armstrong C, Cheng H. Ca2+ blinks: rapid nanoscopic store calcium signaling. Proc Natl Acad Sci USA 2005;102: 3099-3104.
21. Franzini-Armstrong C, Protasi F, Ramesh V. Shape, size, and distribution of Ca(2+) release units and couplons in skeletal and cardiac muscles. Biophys J 1999;77: 1528-1539.
22. Erickson JR, Joiner ML, Guan X, Kutschke W, Yang J, Oddis CV et al. A dynamic pathway for calcium-independent activation of CaMKII by methionine oxidation. Cell 2008;133:462-474.
23. Marx SO, Reiken S, Hisamatsu Y, Jayaraman T, Burkhoff D, Rosemblit N et al. PKA phosphorylation dissociates FKBP12.6 from the calcium release channel (ryanodine receptor): defective regulation in failing hearts. Cell 2000;101:365-376.
24. Bers DM. Cardiac excitation-contraction coupling. Nature 2002;415:198-205.
25. Wang SQ, Wei C, Zhao G, Brochet DX, Shen J, Song LS et al. Imaging microdomain Ca2+ in muscle cells. Circ Res 2004;94:1011-1022.
26. Wallukat G, Morwinski R, Kuhn H. Modulation of the beta-adrenergic response of cardiomyocytes by specific lipoxygenase products involves their incorporation into phosphatidylinositol and activation of protein kinase C. J Biol Chem 1994;269: 29055-29060.
27. Wang D, Patel VV, Ricciotti E, Zhou R, Levin MD, Gao E et al. Cardiomyocyte cyclooxygenase-2 influences cardiac rhythm and function. Proc Natl Acad Sci USA 2009;106:7548-7552.
28. Thum T, Borlak J. Cytochrome P450 mono-oxygenase gene expression and protein activity in cultures of adult cardiomyocytes of the rat. Br J Pharmacol 2000;130: 1745-1752.
29. Gladden JD, Zelickson BR, Wei CC, Ulasova E, Zheng J, Ahmed MI et al. Novel insights into interactions between mitochondria and xanthine oxidase in acute cardiac volume overload. Free Radic Biol Med 2011;51:1975-1984.
30. Minhas KM, Saraiva RM, Schuleri KH, Lehrke S, Zheng M, Saliaris AP et al. Xanthine oxidoreductase inhibition causes reverse remodeling in rats with dilated cardiomyopathy. Circ Res 2006;98:271-279.
31. Seddon M, Shah AM, Casadei B. Cardiomyocytes as effectors of nitric oxide signalling. Cardiovasc Res 2007;75:315-326.
32. Turrens JF. Mitochondrial formation of reactive oxygen species. J Physiol 2003;552: 335-344.
33. Abe J, Berk BC. Reactive oxygen species as mediators of signal transduction in cardiovascular disease. Trends Cardiovasc Med 1998;8:59-64.
34. Murdoch CE, Grieve DJ, Cave AC, Looi YH, Shah AM. NADPH oxidase and heart failure. Curr Opin Pharmacol 2006;6:148-153.
35. Nabeebaccus A, Zhang M, Shah AM. NADPH oxidases and cardiac remodelling. Heart Fail Rev 2011;16:5-12.
36. Cuzzocrea S, Riley DP, Caputi AP, Salvemini D. Antioxidant therapy: a new pharmacological approach in shock, inflammation, and ischemia/reperfusion injury. Pharmacol Rev 2001;53:135-159.
37. Dikalova AE, Bikineyeva AT, Budzyn K, Nazarewicz RR, McCann L, Lewis W et al. Therapeutic targeting of mitochondrial superoxide in hypertension. Circ Res 2010; 107:106-116.
38. Zhao K, Zhao GM, Wu D, Soong Y, Birk AV, Schiller PW et al. Cell-permeable peptide antioxidants targeted to inner mitochondrial membrane inhibit mitochondrial swelling, oxidative cell death, and reperfusion injury. J Biol Chem 2004;279: 34682-34690.
39. St-Pierre J, Buckingham JA, Roebuck SJ, Brand MD. Topology of superoxide production from different sites in the mitochondrial electron transport chain. J Biol Chem 2002;277:44784-44790.
40. Chance B, Sies H, Boveris A. Hydroperoxide metabolism in mammalian organs. Physiol Rev 1979;59:527-605.
41. Barja G. Mitochondrial oxygen radical generation and leak: sites of production in states 4 and 3, organ specificity, and relation to aging and longevity. J Bioenerg Biomembr 1999;31:347-366.
42. Zhao Y, Wang ZB, Xu JX. Effect of cytochrome c on the generation and elimination of O2*-and H2O2 in mitochondria. J Biol Chem 2003;278:2356-2360.
43. Wang W, Fang H, Groom L, Cheng A, Zhang W, Liu J et al. Superoxide flashes in single mitochondria. Cell 2008;134:279-290.
44. Fang H, Chen M, Ding Y, Shang W, Xu J, Zhang X et al. Imaging superoxide flash and metabolism-coupled mitochondrial permeability transition in living animals. Cell Res 2011;21:1295-1304.
45. Li K, Zhang W, Fang H, Xie W, Liu J, Zheng M et al. Superoxide flashes reveal novel properties of mitochondrial reactive oxygen species excitability in cardiomyocytes. Biophys J 2012;102:1011-1021.
46. Wei L, Salahura G, Boncompagni S, Kasischke KA, Protasi F, Sheu SS et al. Mitochondrial superoxide flashes: metabolic biomarkers of skeletal muscle activity and disease. FASEB J 2011;25:3068-3078.
47. Pouvreau S. Superoxide flashes in mouse skeletal muscle are produced by discrete arrays of active mitochondria operating coherently. PLoS One 2010;5.
48. Wang X, Jian C, Zhang X, Huang Z, Xu J, Hou T et al. Superoxide flashes: elemental events of mitochondrial ROS signaling in the heart. J Mol Cell Cardiol 2012;52: 940-948.
49. Fang H, Zhang W, Wang X, Wang W, Li K, Wang Y et al. In vivo imaging of superoxide flashes in skeletal muscle. Biophys J 2009;96:530a.
50. Huang Z, Zhang W, Fang H, Zheng M, Wang X, Xu J et al. Response to 'A critical evaluation of cpYFP as a probe for superoxide'. Free Radic Biol Med 2011;51: 1937-1940.
51. Hou T, Zhang X, Xu J, Jian C, Huang Z, Ye T et al. Synergistic triggering of superoxide flashes by mitochondrial Ca2+ uniport and basal reactive oxygen species elevation. J Biol Chem 2013;288:4602-4612.
52. Hou Y, Ouyang X, Wan RQ, Cheng HP, Mattson MP, Cheng AW. Mitochondrial superoxide production negatively regulates neural progenitor proliferation and cerebral cortical development. Stem Cells 2012;30:2535-2547.
53. Wang JQ, Chen Q, Wang X, Wang QC, Wang Y, Cheng HP et al. Dysregulation of mitochondrial calcium signaling and superoxide flashes cause mitochondrial genomic DNA damage in huntington disease. J Biol Chem 2013;288:3070-3084.
54. Ma Q, Fang H, Shang W, Liu L, Xu Z, Ye T et al. Superoxide flashes: early mitochondrial signals for oxidative stress-induced apoptosis. J Biol Chem 2011;286: 27573-27581.
55. Zorov DB, Filburn CR, Klotz LO, Zweier JL, Sollott SJ. Reactive oxygen species (ROS)-induced ROS release: a new phenomenon accompanying induction of the mitochondrial permeability transition in cardiac myocytes. J Exp Med 2000;192: 1001-1014.
56. Zorov DB, Juhaszova M, Sollott SJ. Mitochondrial ROS-induced ROS release: an update and review. Biochim Biophys Acta 2006;1757:509-517.
57. Ichas F, Mazat JP. From calcium signaling to cell death: two conformations for the mitochondrial permeability transition pore. Switching from low-to highconductance state. Biochim Biophys Acta 1998;1366:33-50.
58. Bernardi P, Forte M. The mitochondrial permeability transition pore. Novartis Found Symp 2007;287:157-164; discussion 64-69.
59. Aon MA, Cortassa S, O'Rourke B. Mitochondrial oscillations in physiology and pathophysiology. Adv Exp Med Biol 2008;641:98-117.
60. Aon MA, Cortassa S, Marban E, O'Rourke B. Synchronized whole cell oscillations in mitochondrial metabolism triggered by a local release of reactive oxygen species in cardiac myocytes. J Biol Chem 2003;278:44735-44744.
61. Yan Y, Liu J, Wei C, Li K, Xie W, Wang Y et al. Bidirectional regulation of Ca2+ sparks by mitochondria-derived reactive oxygen species in cardiac myocytes. Cardiovasc Res 2008;77:432-441.
62. Kurz FT, Aon MA, O'Rourke B, Armoundas AA. Spatio-temporal oscillations of individual mitochondria in cardiac myocytes reveal modulation of synchronized mitochondrial clusters. Proc Natl Acad Sci USA 2010;107:14315-14320.
63. Aon MA, Cortassa S, O'Rourke B. Percolation and criticality in a mitochondrial network. Proc Natl Acad Sci USA 2004;101:4447-4452.
64. Huang X, Sun L, Ji S, Zhao T, ZhangW, Xu J et al. Kissing and nanotunneling mediate intermitochondrial communication in the heart. Proc Natl Acad Sci USA 2013;110: 2846-2851.
65. Baughman JM, Perocchi F, Girgis HS, Plovanich M, Belcher-Timme CA, Sancak Y et al. Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter. Nature 2011;476:341-345.
66. De Stefani D, Raffaello A, Teardo E, Szabo I, Rizzuto R. A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter. Nature 2011;476: 336-340.
67. Kirichok Y, Krapivinsky G, Clapham DE. The mitochondrial calcium uniporter is a highly selective ion channel. Nature 2004;427:360-364.
68. Perocchi F, Gohil VM, Girgis HS, Bao XR, McCombs JE, Palmer AE et al. MICU1 encodes a mitochondrial EF hand protein required for Ca(2+) uptake. Nature 2010;467:291-296.
69. Santo-Domingo J, Demaurex N. Calcium uptake mechanisms of mitochondria. Biochim Biophys Acta 2010;1797:907-912.
70. Miyata H, Silverman HS, Sollott SJ, Lakatta EG, Stern MD, Hansford RG. Measurement of mitochondrial free Ca2+ concentration in living single rat cardiac myocytes. Am J Physiol 1991;261:H1123-1134.
71. Bedard K, Krause KH. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 2007;87:245-313.
72. Prosser BL, Ward CW, Lederer WJ. X-ROS signaling: rapid mechano-chemo transduction in heart. Science 2011;333:1440-1445.
73. Hidalgo C, Sanchez G, Barrientos G, Aracena-Parks P. A transverse tubule NADPH oxidase activity stimulates calcium release from isolated triads via ryanodine receptor type 1 S-glutathionylation. J Biol Chem 2006;281:26473-26482.
74. Feron O, Belhassen L, Kobzik L, Smith TW, Kelly RA, Michel T. Endothelial nitric oxide synthase targeting to caveolae. Specific interactions with caveolin isoforms in cardiac myocytes and endothelial cells. J Biol Chem 1996;271:22810-22814.
75. Fulton D, Fontana J, Sowa G, Gratton JP, Lin M, Li KX et al. Localization of endothelial nitric-oxide synthase phosphorylated on serine 1179 and nitric oxide in Golgi and plasma membrane defines the existence of two pools of active enzyme. J Biol Chem 2002;277:4277-4284.
76. Damy T, Ratajczak P, Shah AM, Camors E, Marty I, Hasenfuss G et al. Increased neuronal nitric oxide synthase-derived NO production in the failing human heart. Lancet 2004;363:1365-1367.
77. Williams JC, Armesilla AL, Mohamed TM, Hagarty CL, McIntyre FH, Schomburg S et al. The sarcolemmal calcium pump, alpha-1 syntrophin, and neuronal nitric-oxide synthase are parts of a macromolecular protein complex. J Biol Chem 2006;281: 23341-23348.
78. Xu KY, Huso DL, Dawson TM, Bredt DS, Becker LC. Nitric oxide synthase in cardiac sarcoplasmic reticulum. Proc Natl Acad Sci USA 1999;96:657-662.
79. Prosser BL, Khairallah RJ, Ziman AP, Ward CW, Lederer WJ. X-ROS signaling in the heart and skeletal muscle: stretch-dependent local ROS regulates [Ca(2+)](i). J Mol Cell Cardiol. Advance Access published Dec 6, 2012, doi:10.1016/j.yjmcc.2012.11.011.
80. Iribe G, Ward CW, Camelliti P, Bollensdorff C, Mason F, Burton RA et al. Axial stretch of rat single ventricular cardiomyocytes causes an acute and transient increase in Ca2+ spark rate. Circ Res 2009;104:787-795.
81. Zima AV, Blatter LA. Redox regulation of cardiac calcium channels and transporters. Cardiovasc Res 2006;71:310-321.
82. Donoso P, Sanchez G, Bull R, Hidalgo C. Modulation of cardiac ryanodine receptor activity by ROS and RNS. Front Biosci 2011;16:553-567.
83. Gen W, Tani M, Takeshita J, Ebihara Y, Tamaki K. Mechanisms of Ca2+ overload induced by extracellular H2O2 in quiescent isolated rat cardiomyocytes. Basic Res Cardiol 2001;96:623-629.
84. Isaeva EV, Shkryl VM, Shirokova N. Mitochondrial redox state and Ca2+ sparks in permeabilized mammalian skeletal muscle. J Physiol 2005;565:855-872.
85. Goldhaber JI, Liu E. Excitation-contraction coupling in single guinea-pig ventricular myocytes exposed to hydrogen peroxide. J Physiol 1994;477(Pt 1):135-147.
86. Zima AV, Copello JA, Blatter LA. Effects of cytosolic NADH/NAD(+) levels on sarcoplasmic reticulum Ca(2+) release in permeabilized rat ventricular myocytes. J Physiol 2004;555:727-741.
87. Wang W, Liu X, Gong G. Cardiac excitation contraction coupling stimulates mitochondrial respiration and superoxide flash activity. BASC05-Best of AHA Specialty Conferences 2011;BCVS 2011.
88. Zhou L, Aon MA, Liu T, O'Rourke B. Dynamic modulation of Ca2+ sparks by mitochondrial oscillations in isolated guinea pig cardiomyocytes under oxidative stress. J Mol Cell Cardiol 2011;51:632-639.
89. Belmonte S, Morad M. 'Pressure-flow'-triggered intracellular Ca2+ transients in rat cardiac myocytes: possible mechanisms and role of mitochondria. J Physiol 2008; 586:1379-1397.
90. Petroff MG, Kim SH, Pepe S, Dessy C, Marban E, Balligand JL et al. Endogenous nitric oxide mechanisms mediate the stretch dependence of Ca2+ release in cardiomyocytes. Nat Cell Biol 2001;3:867-873.
91. Tocchetti CG, Wang W, Froehlich JP, Huke S, Aon MA, Wilson GM et al. Nitroxyl improves cellular heart function by directly enhancing cardiac sarcoplasmic reticulum Ca2+ cycling. Circ Res 2007;100:96-104.
92. Auld BA. Acoustic fields and waves in solid. Melbourne: Krieger, 1990.
93. de Tombe PP, Mateja RD, Tachampa K, Ait Mou Y, Farman GP, Irving TC. Myofilament length dependent activation. J Mol Cell Cardiol 2010;48:851-858.
94. Cingolani HE, Perez NG, Cingolani OH, Ennis IL. The Anrep effect: 100 years later. Am J Physiol Heart Circ Physiol 2013;304:H175-H182.
95. Kentish JC, Wrzosek A. Changes in force and cytosolic Ca2+ concentration after length changes in isolated rat ventricular trabeculae. J Physiol-London 1998;506: 431-444.
96. Xu L, Eu JP, Meissner G, Stamler JS. Activation of the cardiac calcium release channel (ryanodine receptor) by poly-S-nitrosylation. Science 1998;279:234-237.
97. Pessah IN, Kim KH, Feng W. Redox sensing properties of the ryanodine receptor complex. Front Biosci 2002;7:a72-a79.
98. Hidalgo C, Donoso P, Carrasco MA. The ryanodine receptors Ca2+ release channels: cellular redox sensors IUBMB Life 2005;57:315-322.
99. Liu G, Abramson JJ, Zable AC, Pessah IN. Direct evidence for the existence and functional role of hyperreactive sulfhydryls on the ryanodine receptortriadin complex selectively labeled by the coumarin maleimide 7-diethylamino-3-(4′-maleimidylphenyl)-4-methylcoumarin. Mol Pharmacol 1994;45:189-200.
100. Pessah IN, Feng W. Functional role of hyperreactive sulfhydryl moieties within the ryanodine receptor complex. Antioxid Redox Signal 2000;2:17-25.
101. Abramson JJ, Salama G. Critical sulfhydryls regulate calcium release from sarcoplasmic reticulum. J Bioenerg Biomembr 1989;21:283-294.
102. Boraso A, Williams AJ. Modification of the gating of the cardiac sarcoplasmic reticulum Ca(2+)-release channel by H2O2 and dithiothreitol. Am J Physiol 1994;267: H1010-1016.
103. Anzai K, Ogawa K, Kuniyasu A, Ozawa T, Yamamoto H, Nakayama H. Effects of hydroxyl radical and sulfhydryl reagents on the open probability of the purified cardiac ryanodine receptor channel incorporated into planar lipid bilayers. Biochem Biophys Res Commun 1998;249:938-942.
104. Eager KR, Roden LD, Dulhunty AF. Actions of sulfhydryl reagents on single ryanodine receptor Ca(2+)-release channels from sheep myocardium. Am J Physiol 1997;272:C1908-1918.
105. Okabe E, Tsujimoto Y, Kobayashi Y. Calmodulin and cyclic ADP-ribose interaction in Ca2+ signaling related to cardiac sarcoplasmic reticulum: superoxide anion radicaltriggered Ca2+ release. Antioxid Redox Signal 2000;2:47-54.
106. Zhang JZ, Wu Y, Williams BY, Rodney G, Mandel F, Strasburg GM et al. Oxidation of the skeletal muscle Ca2+ release channel alters calmodulin binding. Am J Physiol 1999; 276:C46-53.
107. Smith JS, Rousseau E, Meissner G. Calmodulin modulation of single sarcoplasmic reticulum Ca2+-release channels from cardiac and skeletal muscle. Circ Res 1989;64: 352-359.
108. Kawakami M, Okabe E. Superoxide anion radical-triggered Ca2+ release from cardiac sarcoplasmic reticulum through ryanodine receptor Ca2+ channel. Mol Pharmacol 1998;53:497-503.
109. Marchioli R, Schweiger C, Levantesi G, Tavazzi L, Valagussa F. Antioxidant vitamins and prevention of cardiovascular disease: epidemiological and clinical trial data. Lipids 2001;36(Suppl):S53-S63.
110. El-Hamamsy I, Stevens LM, Carrier M, Pellerin M, Bouchard D, Demers P 2007 Effect of intravenous N-acetylcysteine on outcomes after coronary artery bypass surgery: A randomized, double-blind, placebo-controlled clinical trial J Thorac Cardiovasc Surg 133 7-12.