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Redox balance and cardioprotection

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Abstract

Coronary artery disease is a major cause of morbidity and mortality in the Western countries. Acute myocardial infarction is a serious and often lethal consequence of coronary artery disease, resulting in contractile dysfunction and cell death. It is well known that unbalanced and high steady state levels of reactive oxygen and nitrogen species (ROS/RNS) are responsible for cytotoxicity, which in heart leads to contractile dysfunction and cell death. Pre- and post-conditioning of the myocardium are two treatment strategies that reduce contractile dysfunction and the amount of cell death considerably. Paradoxically, ROS and RNS have been identified as a part of cardioprotective signaling molecules, which are essential in pre- and post-conditioning processes. S-nitrosylation of proteins is a specific posttranslational modification that plays an important role in cardioprotection, especially within mitochondria. In fact, mitochondria are of paramount importance in either promoting or limiting ROS/RNS generation and reperfusion injury, and in triggering kinase activation by ROS/RNS signaling in cardioprotection. These organelles are also the targets of acidosis, which prevents mitochondrial transition pore opening, thus avoiding ROS-induced ROS release. Therefore, we will consider mitochondria as either targets of damage or protection from it. The origin of ROS/RNS and the cardioprotective signaling pathways involved in ROS/RNS-based pre- and post-conditioning will be explored in this article. A particular emphasis will be given to new aspects concerning the processes of S-nitrosylation in the cardioprotective scenario.

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References

  1. Ago T, Kuroda J, Pain J, Fu C, Li H, Sadoshima J (2010) Upregulation of Nox4 by hypertrophic stimuli promotes apoptosis and mitochondrial dysfunction in cardiac myocytes. Circ Res 106:1253–1264. doi:10.1161/CIRCRESAHA.109.213116

    PubMed  CAS  Google Scholar 

  2. Ambrosio G, Tritto I, Chiariello M (1995) The role of oxygen free radicals in preconditioning. J Mol Cell Cardiol 27:1035–1039 0022-2828(95)90072-1

    PubMed  CAS  Google Scholar 

  3. Andreka P, Zang J, Dougherty C, Slepak TI, Webster KA, Bishopric NH (2001) Cytoprotection by Jun kinase during nitric oxide-induced cardiac myocyte apoptosis. Circ Res 88:305–312. doi:10.1161/01.RES.88.3.305

    PubMed  CAS  Google Scholar 

  4. Argaud L, Gateau-Roesch O, Augeul L, Couture-Lepetit E, Loufouat J, Gomez L, Robert D, Ovize M (2008) Increased mitochondrial calcium coexists with decreased reperfusion injury in postconditioned (but not preconditioned) hearts. Am J Physiol Heart Circ Physiol 294:H386–H391. doi:10.1152/ajpheart.01035.2007

    PubMed  CAS  Google Scholar 

  5. Avkiran M, Ibuki C (1992) Reperfusion-induced arrhythmias. A role for washout of extracellular protons? Circ Res 71:1429–1440. doi:10.1161/01.RES.71.6.1429

    PubMed  CAS  Google Scholar 

  6. Baba SP, Wetzelberger K, Hoetker JD, Bhatnagar A (2009) Posttranslational glutathiolation of aldose reductase (AKR1B1): a possible mechanism of protein recovery from S-nitrosylation. Chem Biol Interact 178:250–258. doi:10.1016/j.cbi.2008.11.007

    PubMed  CAS  Google Scholar 

  7. Baines CP (2007) The mitochondrial permeability transition pore as a target of cardioprotective signaling. Am J Physiol Heart Circ Physiol 293:H903–H904. doi:10.1152/ajpheart.00575.2007

    PubMed  CAS  Google Scholar 

  8. Baines CP, Kaiser RA, Sheiko T, Craigen WJ, Molkentin JD (2007) Voltage-dependent anion channels are dispensable for mitochondrial-dependent cell death. Nat Cell Biol 9:550–555. doi:10.1038/ncb1575

    PubMed  CAS  Google Scholar 

  9. Balafanova Z, Bolli R, Zhang J, Zheng Y, Pass JM, Bhatnagar A, Tang XL, Wang O, Cardwell E, Ping P (2002) Nitric oxide (NO) induces nitration of protein kinase Cepsilon (PKCepsilon), facilitating PKCepsilon translocation via enhanced PKCepsilon -RACK2 interactions: a novel mechanism of no-triggered activation of PKCepsilon. J Biol Chem 277:15021–15027. doi:10.1074/jbc.M112451200

    PubMed  CAS  Google Scholar 

  10. Becker L (2004) New concepts in reactive oxygen species and cardiovascular reperfusion physiology. Cardiovasc Res 61:461–470. doi:10.1016/j.cardiores.2003.10.025

    PubMed  CAS  Google Scholar 

  11. Bedard K, Krause KH (2007) The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 87:245–313. doi:10.1152/physrev.00044.2005

    PubMed  CAS  Google Scholar 

  12. Beigi F, Gonzalez DR, Minhas KM, Sun QA, Foster MW, Khan SA, Treuer AV, Dulce RA, Harrison RW, Saraiva RM, Premer C, Schulman IH, Stamler JS, Hare JM (2012) Dynamic denitrosylation via S-nitrosoglutathione reductase regulates cardiovascular function. Proc Natl Acad Sci USA 109:4314–4319. doi:10.1073/pnas.1113319109

    PubMed  CAS  Google Scholar 

  13. Bell RM, Cave AC, Johar S, Hearse DJ, Shah AM, Shattock MJ (2005) Pivotal role of NOX-2-containing NADPH oxidase in early ischemic preconditioning. FASEB J Off Publ Fed Am Soc Exp Biol 19:2037–2039. doi:10.1096/fj.04-2774fje

    CAS  Google Scholar 

  14. Bell RM, Kunuthur SP, Hendry C, Bruce-Hickman D, Davidson S, Yellon DM (2013) Matrix metalloproteinase inhibition protects CyPD knockout mice independently of RISK/mPTP signalling: a parallel pathway to protection. Basic Res Cardiol 108:331. doi:10.1007/s00395-013-0331-7

    PubMed  Google Scholar 

  15. Bendall JK, Cave AC, Heymes C, Gall N, Shah AM (2002) Pivotal role of a gp91(phox)-containing NADPH oxidase in angiotensin II-induced cardiac hypertrophy in mice. Circulation 105:293–296. doi:10.1161/hc0302.103712

    PubMed  CAS  Google Scholar 

  16. Bernabe JC, Tejedo JR, Rincon P, Cahuana GM, Ramirez R, Sobrino F, Bedoya FJ (2001) Sodium nitroprusside-induced mitochondrial apoptotic events in insulin-secreting RINm5F cells are associated with MAP kinases activation. Exp Cell Res 269:222–229. doi:10.1006/excr.2001.5315

    PubMed  CAS  Google Scholar 

  17. Boengler K, Dodoni G, Rodriguez-Sinovas A, Cabestrero A, Ruiz-Meana M, Gres P, Konietzka I, Lopez-Iglesias C, Garcia-Dorado D, Di Lisa F, Heusch G, Schulz R (2005) Connexin 43 in cardiomyocyte mitochondria and its increase by ischemic preconditioning. Cardiovasc Res 67:234–244. doi:10.1016/j.cardiores.2005.04.014

    PubMed  CAS  Google Scholar 

  18. Boengler K, Heusch G, Schulz R (2011) Mitochondria in postconditioning. Antioxid Redox Signal 14:863–880. doi:10.1089/ars.2010.3309

    PubMed  CAS  Google Scholar 

  19. Boengler K, Konietzka I, Buechert A, Heinen Y, Garcia-Dorado D, Heusch G, Schulz R (2007) Loss of ischemic preconditioning’s cardioprotection in aged mouse hearts is associated with reduced gap junctional and mitochondrial levels of connexin 43. Am J Physiol Heart Circ Physiol 292:H1764–H1769. doi:10.1152/ajpheart.01071.2006

    PubMed  CAS  Google Scholar 

  20. Boengler K, Ruiz-Meana M, Gent S, Ungefug E, Soetkamp D, Miro-Casas E, Cabestrero A, Fernandez-Sanz C, Semenzato M, Di Lisa F, Rohrbach S, Garcia-Dorado D, Heusch G, Schulz R (2012) Mitochondrial connexin 43 impacts on respiratory complex I activity and mitochondrial oxygen consumption. J Cell Mol Med 16:1649–1655. doi:10.1111/j.1582-4934.2011.01516.x

    PubMed  CAS  Google Scholar 

  21. Bolli R (1998) Why myocardial stunning is clinically important. Basic Res Cardiol 93:169–172

    PubMed  CAS  Google Scholar 

  22. Bolli R, Dawn B, Tang XL, Qiu Y, Ping P, Xuan YT, Jones WK, Takano H, Guo Y, Zhang J (1998) The nitric oxide hypothesis of late preconditioning. Basic Res Cardiol 93:325–338

    PubMed  CAS  Google Scholar 

  23. Bononi A, Agnoletto C, De Marchi E, Marchi S, Patergnani S, Bonora M, Giorgi C, Missiroli S, Poletti F, Rimessi A, Pinton P (2011) Protein kinases and phosphatases in the control of cell fate. Enzyme Res 2011:329098. doi:10.4061/2011/329098

    PubMed  Google Scholar 

  24. Boveris A, Valdez LB, Zaobornyj T, Bustamante J (2006) Mitochondrial metabolic states regulate nitric oxide and hydrogen peroxide diffusion to the cytosol. Biochim Biophys Acta 1757:535–542. doi:10.1016/j.bbabio.2006.02.010

    PubMed  CAS  Google Scholar 

  25. Brady NR, Hamacher-Brady A, Westerhoff HV, Gottlieb RA (2006) A wave of reactive oxygen species (ROS)-induced ROS release in a sea of excitable mitochondria. Antioxid Redox Signal 8:1651–1665. doi:10.1089/ars.2006.8.1651

    PubMed  CAS  Google Scholar 

  26. Brandes RP, Weissmann N, Schroder K (2010) NADPH oxidases in cardiovascular disease. Free Radic Biol Med 49:687–706. doi:10.1016/j.freeradbiomed.2010.04.030

    PubMed  CAS  Google Scholar 

  27. Brewer AC, Mustafi SB, Murray TV, Rajasekaran NS, Benjamin IJ (2013) Reductive stress linked to small HSPs, G6PD, and Nrf2 pathways in heart disease. Antioxid Redox Signal 18:1114–1127. doi:10.1089/ars.2012.4914

    PubMed  CAS  Google Scholar 

  28. Brown DI, Griendling KK (2009) Nox proteins in signal transduction. Free Radic Biol Med 47:1239–1253. doi:10.1016/j.freeradbiomed.2009.07.023

    PubMed  CAS  Google Scholar 

  29. Burwell LS, Nadtochiy SM, Tompkins AJ, Young S, Brookes PS (2006) Direct evidence for S-nitrosation of mitochondrial complex I. Biochem J 394:627–634. doi:10.1042/BJ20051435

    PubMed  CAS  Google Scholar 

  30. Byrne JA, Grieve DJ, Bendall JK, Li JM, Gove C, Lambeth JD, Cave AC, Shah AM (2003) Contrasting roles of NADPH oxidase isoforms in pressure-overload versus angiotensin II-induced cardiac hypertrophy. Circ Res 93:802–805. doi:10.1161/01.RES.0000099504.30207.F5

    PubMed  CAS  Google Scholar 

  31. Canton M, Skyschally A, Menabo R, Boengler K, Gres P, Schulz R, Haude M, Erbel R, Di Lisa F, Heusch G (2006) Oxidative modification of tropomyosin and myocardial dysfunction following coronary microembolization. Eur Heart J 27:875–881. doi:10.1093/eurheartj/ehi751

    PubMed  CAS  Google Scholar 

  32. Cao Z, Liu L, Van Winkle DM (2005) Met5-enkephalin-induced cardioprotection occurs via transactivation of EGFR and activation of PI3K. Am J Physiol Heart Circ Physiol 288:H1955–H1964. doi:10.1152/ajpheart.00256.2004

    PubMed  CAS  Google Scholar 

  33. Cappello S, Angelone T, Tota B, Pagliaro P, Penna C, Rastaldo R, Corti A, Losano G, Cerra MC (2007) Human recombinant chromogranin A-derived vasostatin-1 mimics preconditioning via an adenosine/nitric oxide signaling mechanism. Am J Physiol Heart Circ Physiol 293:H719–H727. doi:10.1152/ajpheart.01352.2006

    PubMed  CAS  Google Scholar 

  34. Carnicer R, Crabtree MJ, Sivakumaran V, Casadei B, Kass DA (2013) Nitric oxide synthases in heart failure. Antioxid Redox Signal 18:1078–1099. doi:10.1089/ars.2012.4824

    PubMed  CAS  Google Scholar 

  35. Castello PR, David PS, McClure T, Crook Z, Poyton RO (2006) Mitochondrial cytochrome oxidase produces nitric oxide under hypoxic conditions: implications for oxygen sensing and hypoxic signaling in eukaryotes. Cell Metab 3:277–287. doi:10.1016/j.cmet.2006.02.011

    PubMed  CAS  Google Scholar 

  36. Cave AC, Brewer AC, Narayanapanicker A, Ray R, Grieve DJ, Walker S, Shah AM (2006) NADPH oxidases in cardiovascular health and disease. Antioxid Redox Signal 8:691–728. doi:10.1089/ars.2006.8.691

    PubMed  CAS  Google Scholar 

  37. Chen K, Craige SE, Keaney JF Jr (2009) Downstream targets and intracellular compartmentalization in Nox signaling. Antioxid Redox Signal 11:2467–2480. doi:10.1089/ARS.2009.2594

    PubMed  CAS  Google Scholar 

  38. Chen Q, Hoppel CL, Lesnefsky EJ (2006) Blockade of electron transport before cardiac ischemia with the reversible inhibitor amobarbital protects rat heart mitochondria. J Pharmacol Exp Ther 316:200–207. doi:10.1124/jpet.105.091702

    PubMed  CAS  Google Scholar 

  39. Clerk A, Fuller SJ, Michael A, Sugden PH (1998) Stimulation of “stress-regulated” mitogen-activated protein kinases (stress-activated protein kinases/c-Jun N-terminal kinases and p38-mitogen-activated protein kinases) in perfused rat hearts by oxidative and other stresses. J Biol Chem 273:7228–7234. doi:10.1074/jbc.273.13.7228

    PubMed  CAS  Google Scholar 

  40. Clerk A, Michael A, Sugden PH (1998) Stimulation of multiple mitogen-activated protein kinase sub-families by oxidative stress and phosphorylation of the small heat shock protein, HSP25/27, in neonatal ventricular myocytes. Biochem J 333:581–589

    PubMed  CAS  Google Scholar 

  41. Cohen MV, Baines CP, Downey JM (2000) Ischemic preconditioning: from adenosine receptor to KATP channel. Annu Rev Physiol 62:79–109. doi:10.1146/annurev.physiol.62.1.79

    PubMed  CAS  Google Scholar 

  42. Cohen MV, Downey JM (2008) Adenosine: trigger and mediator of cardioprotection. Basic Res Cardiol 103:203–215. doi:10.1007/s00395-007-0687-7

    PubMed  CAS  Google Scholar 

  43. Cohen MV, Downey JM (2011) Ischemic postconditioning: from receptor to end-effector. Antioxid Redox Signal 14:821–831. doi:10.1089/ars.2010.3318

    PubMed  CAS  Google Scholar 

  44. Cohen MV, Yang XM, Downey JM (2008) Acidosis, oxygen, and interference with mitochondrial permeability transition pore formation in the early minutes of reperfusion are critical to postconditioning’s success. Basic Res Cardiol 103:464–471. doi:10.1007/s00395-008-0737-9

    PubMed  Google Scholar 

  45. Cohen MV, Yang XM, Downey JM (2007) The pH hypothesis of postconditioning: staccato reperfusion reintroduces oxygen and perpetuates myocardial acidosis. Circulation 115:1895–1903. doi:10.1161/CIRCULATIONAHA.106.675710

    PubMed  Google Scholar 

  46. Conrad M, Jakupoglu C, Moreno SG, Lippl S, Banjac A, Schneider M, Beck H, Hatzopoulos AK, Just U, Sinowatz F, Schmahl W, Chien KR, Wurst W, Bornkamm GW, Brielmeier M (2004) Essential role for mitochondrial thioredoxin reductase in hematopoiesis, heart development, and heart function. Mol Cell Biol 24:9414–9423. doi:10.1128/MCB.24.21.9414-9423.2004

    PubMed  CAS  Google Scholar 

  47. Costa AD, Garlid KD (2008) Intramitochondrial signaling: interactions among mitoKATP, PKCepsilon, ROS, and MPT. Am J Physiol Heart Circ Physiol 295:H874–H882. doi:10.1152/ajpheart.01189.2007

    PubMed  CAS  Google Scholar 

  48. Cox AG, Winterbourn CC, Hampton MB (2010) Mitochondrial peroxiredoxin involvement in antioxidant defence and redox signalling. Biochem J 425:313–325. doi:10.1042/BJ20091541

    CAS  Google Scholar 

  49. Crisafulli A, Melis F, Tocco F, Santoboni UM, Lai C, Angioy G, Lorrai L, Pittau G, Concu A, Pagliaro P (2004) Exercise-induced and nitroglycerin-induced myocardial preconditioning improves hemodynamics in patients with angina. Am J Physiol Heart Circ Physiol 287:H235–H242. doi:10.1152/ajpheart.00989.2003

    PubMed  CAS  Google Scholar 

  50. Dai DF, Santana LF, Vermulst M, Tomazela DM, Emond MJ, MacCoss MJ, Gollahon K, Martin GM, Loeb LA, Ladiges WC, Rabinovitch PS (2009) Overexpression of catalase targeted to mitochondria attenuates murine cardiac aging. Circulation 119:2789–2797. doi:10.1161/CIRCULATIONAHA.108.822403

    PubMed  CAS  Google Scholar 

  51. Das M, Gherghiceanu M, Lekli I, Mukherjee S, Popescu LM, Das DK (2008) Essential role of lipid raft in ischemic preconditioning. Cell Physiol Biochem 21:325–334. doi:10.1159/000129391

    PubMed  CAS  Google Scholar 

  52. Dawn B, Bolli R (2002) Role of nitric oxide in myocardial preconditioning. Ann N Y Acad Sci 962:18–41. doi:10.1111/j.1749-6632.2002.tb04053.x

    PubMed  CAS  Google Scholar 

  53. Deora AA, Hajjar DP, Lander HM (2000) Recruitment and activation of Raf-1 kinase by nitric oxide-activated Ras. Biochemistry 39:9901–9908. doi:10.1021/bi992954b

    PubMed  CAS  Google Scholar 

  54. Di Lisa F, Canton M, Carpi A, Kaludercic N, Menabo R, Menazza S, Semenzato M (2011) Mitochondrial injury and protection in ischemic pre- and postconditioning. Antioxid Redox Signal 14:881–891. doi:10.1089/ars.2010.3375

    PubMed  Google Scholar 

  55. Dikalov SI, Dikalova AE, Bikineyeva AT, Schmidt HH, Harrison DG, Griendling KK (2008) Distinct roles of Nox1 and Nox4 in basal and angiotensin II-stimulated superoxide and hydrogen peroxide production. Free Radic Biol Med 45:1340–1351. doi:10.1016/j.freeradbiomed.2008.08.013

    PubMed  CAS  Google Scholar 

  56. Dost T, Cohen MV, Downey JM (2008) Redox signaling triggers protection during the reperfusion rather than the ischemic phase of preconditioning. Basic Res Cardiol 103:378–384. doi:10.1007/s00395-008-0718-z

    PubMed  Google Scholar 

  57. Downey JM, Cohen MV (2006) A really radical observation—a comment on Penna et al. in Basic Res Cardiol (2006) 101:180–189. Basic Res Cardiol 101:190–191. doi:10.1007/s00395-006-0586-3

    PubMed  Google Scholar 

  58. Droge W (2002) Free radicals in the physiological control of cell function. Physiol Rev 82:47–95. doi:10.1152/physrev.00018.2001

    PubMed  CAS  Google Scholar 

  59. Duquesnes N, Lezoualc’h F, Crozatier B (2011) PKC-delta and PKC-epsilon: foes of the same family or strangers? J Mol Cell Cardiol 51:665–673. doi:10.1016/j.yjmcc.2011.07.013

    PubMed  CAS  Google Scholar 

  60. Ferdinandy P, Schulz R (2003) Nitric oxide, superoxide, and peroxynitrite in myocardial ischaemia-reperfusion injury and preconditioning. Br J Pharmacol 138:532–543. doi:10.1038/sj.bjp.0705080

    PubMed  CAS  Google Scholar 

  61. Finkel T (1999) Signal transduction by reactive oxygen species in non-phagocytic cells. J Leukoc Biol 65:337–340

    PubMed  CAS  Google Scholar 

  62. Forbes RA, Steenbergen C, Murphy E (2001) Diazoxide-induced cardioprotection requires signaling through a redox-sensitive mechanism. Circ Res 88:802–809. doi:10.1161/hh0801.089342

    PubMed  CAS  Google Scholar 

  63. Forster K, Kuno A, Solenkova N, Felix SB, Krieg T (2007) The delta-opioid receptor agonist DADLE at reperfusion protects the heart through activation of pro-survival kinases via EGF receptor transactivation. Am J Physiol Heart Circ Physiol 293:H1604–H1608. doi:10.1152/ajpheart.00418.2007

    PubMed  Google Scholar 

  64. Foster DB, Ho AS, Rucker J, Garlid AO, Chen L, Sidor A, Garlid KD, O’Rourke B (2012) Mitochondrial ROMK channel is a molecular component of mitoK(ATP). Circ Res 111:446–454. doi:10.1161/CIRCRESAHA.112.266445

    PubMed  CAS  Google Scholar 

  65. Galagudza M, Kurapeev D, Minasian S, Valen G, Vaage J (2004) Ischemic postconditioning: brief ischemia during reperfusion converts persistent ventricular fibrillation into regular rhythm. Eur J Cardiothorac Surg 25:1006–1010. doi:10.1016/j.ejcts.2004.02.003

    PubMed  Google Scholar 

  66. Garlid AO, Jaburek M, Jacobs JP, Garlid KD (2013) Mitochondrial Reactive Oxygen Species - Which ROS Signals Cardioprotection? Am J Physiol Heart Circ Physiol 305:H960–H968. doi:10.1152/ajpheart.00858.2012

    PubMed  CAS  Google Scholar 

  67. Gattullo D, Linden RJ, Losano G, Pagliaro P, Westerhof N (1999) Ischaemic preconditioning changes the pattern of coronary reactive hyperaemia in the goat: role of adenosine and nitric oxide. Cardiovasc Res 42:57–64. doi:10.1016/S0008-6363(98)00319-8

    PubMed  CAS  Google Scholar 

  68. Gho BC, Schoemaker RG, van den Doel MA, Duncker DJ, Verdouw PD (1996) Myocardial protection by brief ischemia in noncardiac tissue. Circulation 94:2193–2200. doi:10.1161/01.CIR.94.9.2193

    PubMed  CAS  Google Scholar 

  69. Giricz Z, Gorbe A, Pipis J, Burley DS, Ferdinandy P, Baxter GF (2009) Hyperlipidaemia induced by a high-cholesterol diet leads to the deterioration of guanosine-3′,5′-cyclic monophosphate/protein kinase G-dependent cardioprotection in rats. Br J Pharmacol 158:1495–1502. doi:10.1111/j.1476-5381.2009.00424.x

    PubMed  CAS  Google Scholar 

  70. Gottlieb RA, Finley KD, Mentzer RM Jr (2009) Cardioprotection requires taking out the trash. Basic Res Cardiol 104:169–180. doi:10.1007/s00395-009-0011-9

    PubMed  Google Scholar 

  71. Gow AJ, Duran D, Malcolm S, Ischiropoulos H (1996) Effects of peroxynitrite-induced protein modifications on tyrosine phosphorylation and degradation. FEBS Lett 385:63–66. doi:10.116/0014-5793(96)00347-X

    PubMed  CAS  Google Scholar 

  72. Granata R, Trovato L, Gallo MP, Destefanis S, Settanni F, Scarlatti F, Brero A, Ramella R, Volante M, Isgaard J, Levi R, Papotti M, Alloatti G, Ghigo E (2009) Growth hormone-releasing hormone promotes survival of cardiac myocytes in vitro and protects against ischaemia-reperfusion injury in rat heart. Cardiovasc Res 83:303–312. doi:10.1093/cvr/cvp090

    PubMed  CAS  Google Scholar 

  73. Grech ED, Ramsdale DR (1994) Termination of reperfusion arrhythmia by coronary artery occlusion. Br Heart J 72:94–95. doi:10.1136/hrt.72.1.94

    PubMed  CAS  Google Scholar 

  74. Guo Y, Sanganalmath SK, Wu W, Zhu X, Huang Y, Tan W, Ildstad ST, Li Q, Bolli R (2012) Identification of inducible nitric oxide synthase in peripheral blood cells as a mediator of myocardial ischemia/reperfusion injury. Basic Res Cardiol 107:253. doi:10.1007/s00395-012-0253-9

    PubMed  Google Scholar 

  75. Hafstad AD, Nabeebaccus AA, Shah AM (2013) Novel aspects of ROS signalling in heart failure. Basic Res Cardiol 108:359. doi:10.1007/s00395-013-0359-8

    PubMed  Google Scholar 

  76. Hausenloy D, Wynne A, Duchen M, Yellon D (2004) Transient mitochondrial permeability transition pore opening mediates preconditioning-induced protection. Circulation 109:1714–1717. doi:10.1161/01.CIR.0000126294.81407.7D

    PubMed  CAS  Google Scholar 

  77. Hausenloy DJ, Boston-Griffiths EA, Yellon DM (2012) Cyclosporin A and cardioprotection: from investigative tool to therapeutic agent. Br J Pharmacol 165:1235–1245. doi:10.1111/j.1476-5381.2011.01700.x

    PubMed  CAS  Google Scholar 

  78. Hausenloy DJ, Lecour S, Yellon DM (2011) Reperfusion injury salvage kinase and survivor activating factor enhancement prosurvival signaling pathways in ischemic postconditioning: two sides of the same coin. Antioxid Redox Signal 14:893–907. doi:10.1089/ars.2010.3360

    PubMed  CAS  Google Scholar 

  79. Hausenloy DJ, Lim SY, Ong SG, Davidson SM, Yellon DM (2010) Mitochondrial cyclophilin-D as a critical mediator of ischaemic preconditioning. Cardiovasc Res 88:67–74. doi:10.1093/cvr/cvq113

    PubMed  CAS  Google Scholar 

  80. Hausenloy DJ, Ong SB, Yellon DM (2009) The mitochondrial permeability transition pore as a target for preconditioning and postconditioning. Basic Res Cardiol 104:189–202. doi:10.1007/s00395-009-0010-x

    PubMed  CAS  Google Scholar 

  81. Hausenloy DJ, Wynne AM, Yellon DM (2007) Ischemic preconditioning targets the reperfusion phase. Basic Res Cardiol 102:445–452. doi:10.1007/s00395-007-0656-1

    PubMed  CAS  Google Scholar 

  82. Hausenloy DJ, Yellon DM (2008) Remote ischaemic preconditioning: underlying mechanisms and clinical application. Cardiovasc Res 79:377–386. doi:10.1093/cvr/cvn114

    PubMed  CAS  Google Scholar 

  83. Heinzel FR, Luo Y, Dodoni G, Boengler K, Petrat F, Di Lisa F, de Groot H, Schulz R, Heusch G (2006) Formation of reactive oxygen species at increased contraction frequency in rat cardiomyocytes. Cardiovasc Res 71:374–382. doi:10.1016/j.cardiores.2006.05.014

    PubMed  CAS  Google Scholar 

  84. Heinzel FR, Luo Y, Li X, Boengler K, Buechert A, Garcia-Dorado D, Di Lisa F, Schulz R, Heusch G (2005) Impairment of diazoxide-induced formation of reactive oxygen species and loss of cardioprotection in connexin 43 deficient mice. Circ Res 97:583–586. doi:10.1161/01.RES.0000181171.65293.65

    PubMed  CAS  Google Scholar 

  85. Hendgen-Cotta UB, Merx MW, Shiva S, Schmitz J, Becher S, Klare JP, Steinhoff HJ, Goedecke A, Schrader J, Gladwin MT, Kelm M, Rassaf T (2008) Nitrite reductase activity of myoglobin regulates respiration and cellular viability in myocardial ischemia-reperfusion injury. Proc Natl Acad Sci USA 105:10256–10261. doi:10.1073/pnas.0801336105

    PubMed  CAS  Google Scholar 

  86. Heusch G (2013) Cardioprotection: chances and challenges of its translation to the clinic. Lancet 381:166–175. doi:10.1016/S0140-6736(12)60916-7

    PubMed  Google Scholar 

  87. Heusch G (2009) No risk, no… cardioprotection? A critical perspective. Cardiovasc Res 84:173–175. doi:10.1093/cvr/cvp298

    PubMed  CAS  Google Scholar 

  88. Heusch G, Boengler K, Schulz R (2010) Inhibition of mitochondrial permeability transition pore opening: the Holy Grail of cardioprotection. Basic Res Cardiol 105:151–154. doi:10.1007/s00395-009-0080-9

    PubMed  Google Scholar 

  89. Heusch G, Musiolik J, Gedik N, Skyschally A (2011) Mitochondrial STAT3 activation and cardioprotection by ischemic postconditioning in pigs with regional myocardial ischemia/reperfusion. Circ Res 109:1302–1308. doi:10.1161/CIRCRESAHA.111.255604

    PubMed  CAS  Google Scholar 

  90. Heusch G, Schulz R (2011) Preservation of peripheral vasodilation as a surrogate of cardioprotection? The mechanistic role of ATP-dependent potassium channels and the mitochondrial permeability transition pore. Eur Heart J 32:1184–1186. doi:10.1093/eurheartj/ehq511

    PubMed  Google Scholar 

  91. Heusch G, Schulz R (2011) A radical view on the contractile machinery in human heart failure. J Am Coll Cardiol 57:310–312. doi:10.1016/j.jacc.2010.06.057

    PubMed  CAS  Google Scholar 

  92. Holmuhamedov EL, Oberlin A, Short K, Terzic A, Jahangir A (2012) Cardiac subsarcolemmal and interfibrillar mitochondria display distinct responsiveness to protection by diazoxide. PLoS ONE 7:e44667. doi:10.1371/journal.pone.0044667

    PubMed  CAS  Google Scholar 

  93. Hu S, Dong H, Zhang H, Wang S, Hou L, Chen S, Zhang J, Xiong L (2012) Noninvasive limb remote ischemic preconditioning contributes neuroprotective effects via activation of adenosine A1 receptor and redox status after transient focal cerebral ischemia in rats. Brain Res 1459:81–90. doi:10.1016/j.brainres.2012.04.017

    PubMed  CAS  Google Scholar 

  94. Huang J, Lam GY, Brumell JH (2011) Autophagy signaling through reactive oxygen species. Antioxid Redox Signal 14:2215–2231. doi:10.1089/ars.2010.3554

    PubMed  CAS  Google Scholar 

  95. Ibuki C, Hearse DJ, Avkiran M (1993) Mechanisms of antifibrillatory effect of acidic reperfusion: role of perfusate bicarbonate concentration. Am J Physiol 264:H783–H790

    PubMed  CAS  Google Scholar 

  96. Iliodromitis EK, Georgiadis M, Cohen MV, Downey JM, Bofilis E, Kremastinos DT (2006) Protection from post-conditioning depends on the number of short ischemic insults in anesthetized pigs. Basic Res Cardiol 101:502–507. doi:10.1007/s00395-006-0606-3

    PubMed  Google Scholar 

  97. Inserte J, Ruiz-Meana M, Rodriguez-Sinovas A, Barba I, Garcia-Dorado D (2011) Contribution of delayed intracellular pH recovery to ischemic postconditioning protection. Antioxid Redox Signal 14:923–939. doi:10.1089/ars.2010.3312

    PubMed  CAS  Google Scholar 

  98. Ivanes F, Rioufol G, Piot C, Ovize M (2011) Postconditioning in acute myocardial infarction patients. Antioxid Redox Signal 14:811–820. doi:10.1089/ars.2010.3354

    PubMed  CAS  Google Scholar 

  99. Johnson JA, Gray MO, Chen CH, Mochly-Rosen D (1996) A protein kinase C translocation inhibitor as an isozyme-selective antagonist of cardiac function. J Biol Chem 271:24962–24966. doi:10.1074/jbc.271.40.24962

    PubMed  CAS  Google Scholar 

  100. Jourd’heuil D, Lancaster JR, Jr., Fukuto J, Roberts DD, Miranda KM, Mayer B, Grisham MB, Wink DA (2010) The bell-shaped curve for peroxynitrite-mediated oxidation and nitration of NO/O2 −* is alive and well. J Biol Chem 285:le15; author reply le16 doi:10.1074/jbc.L110.110080

  101. Jourd’heuil D, Laroux FS, Miles AM, Wink DA, Grisham MB (1999) Effect of superoxide dismutase on the stability of S-nitrosothiols. Arch Biochem Biophys 361:323–330. doi:10.1006/abbi.1998.1010

    PubMed  Google Scholar 

  102. Kawamura S, Yoshida K, Miura T, Mizukami Y, Matsuzaki M (1998) Ischemic preconditioning translocates PKC-δ and -ε, which mediate functional protection in isolated rat heart. Am J Physiol 275:H2266–H2271

    PubMed  CAS  Google Scholar 

  103. Kin H, Zatta AJ, Lofye MT, Amerson BS, Halkos ME, Kerendi F, Zhao ZQ, Guyton RA, Headrick JP, Vinten-Johansen J (2005) Postconditioning reduces infarct size via adenosine receptor activation by endogenous adenosine. Cardiovasc Res 67:124–133. doi:10.1016/j.cardiores.2005.02.015

    PubMed  CAS  Google Scholar 

  104. Kin H, Zhao ZQ, Sun HY, Wang NP, Corvera JS, Halkos ME, Kerendi F, Guyton RA, Vinten-Johansen J (2004) Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion. Cardiovasc Res 62:74–85. doi:10.1016/j.cardiores.2004.01.006

    PubMed  CAS  Google Scholar 

  105. Kloner RA, Dow J, Bhandari A (2006) Postconditioning markedly attenuates ventricular arrhythmias after ischemia-reperfusion. J Cardiovasc Pharmacol Ther 11:55–63. doi:10.1177/107424840601100105

    PubMed  Google Scholar 

  106. Kohr MJ, Aponte AM, Sun J, Wang G, Murphy E, Gucek M, Steenbergen C (2011) Characterization of potential S-nitrosylation sites in the myocardium. Am J Physiol Heart Circ Physiol 300:H1327–H1335. doi:10.1152/ajpheart.00997.2010

    PubMed  CAS  Google Scholar 

  107. Kokoszka JE, Waymire KG, Levy SE, Sligh JE, Cai J, Jones DP, MacGregor GR, Wallace DC (2004) The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore. Nature 427:461–465. doi:10.1038/nature02229

    PubMed  CAS  Google Scholar 

  108. Kong SK, Yim MB, Stadtman ER, Chock PB (1996) Peroxynitrite disables the tyrosine phosphorylation regulatory mechanism: lymphocyte-specific tyrosine kinase fails to phosphorylate nitrated cdc2(6-20)NH2 peptide. Proc Natl Acad Sci USA 93:3377–3382

    PubMed  CAS  Google Scholar 

  109. Konishi H, Tanaka M, Takemura Y, Matsuzaki H, Ono Y, Kikkawa U, Nishizuka Y (1997) Activation of protein kinase C by tyrosine phosphorylation in response to H2O2. Proc Natl Acad Sci USA 94:11233–11237. doi:10.1073/pnas.111158798

    PubMed  CAS  Google Scholar 

  110. Korichneva I, Hoyos B, Chua R, Levi E, Hammerling U (2002) Zinc release from protein kinase C as the common event during activation by lipid second messenger or reactive oxygen. J Biol Chem 277:44327–44331. doi:10.1074/jbc.M205634200

    PubMed  CAS  Google Scholar 

  111. Kornmann B, Currie E, Collins SR, Schuldiner M, Nunnari J, Weissman JS, Walter P (2009) An ER-mitochondria tethering complex revealed by a synthetic biology screen. Science 325:477–481. doi:10.1126/science.1175088

    PubMed  CAS  Google Scholar 

  112. Kostyak JC, Hunter JC, Korzick DH (2006) Acute PKCdelta inhibition limits ischaemia-reperfusion injury in the aged rat heart: role of GSK-3beta. Cardiovasc Res 70:325–334. doi:10.1016/j.cardiores.2006.02.009

    PubMed  CAS  Google Scholar 

  113. Kowaltowski AJ, de Souza-Pinto NC, Castilho RF, Vercesi AE (2009) Mitochondria and reactive oxygen species. Free Radic Biol Med 47:333–343. doi:10.1016/j.freeradbiomed.2009.05.004

    PubMed  CAS  Google Scholar 

  114. Krieg T, Qin Q, McIntosh EC, Cohen MV, Downey JM (2002) ACh and adenosine activate PI3-kinase in rabbit hearts through transactivation of receptor tyrosine kinases. Am J Physiol Heart Circ Physiol 283:H2322–H2330. doi:10.1152/ajpheart.00474.2002

    PubMed  CAS  Google Scholar 

  115. Kuno A, Critz SD, Cohen MV, Downey JM (2007) Nicorandil opens mitochondrial K(ATP) channels not only directly but also through a NO-PKG-dependent pathway. Basic Res Cardiol 102:73–79. doi:10.1007/s00395-006-0612-5

    PubMed  CAS  Google Scholar 

  116. Kupai K, Csonka C, Fekete V, Odendaal L, van Rooyen J, de Marais W, Csont T, Ferdinandy P (2009) Cholesterol diet-induced hyperlipidemia impairs the cardioprotective effect of postconditioning: role of peroxynitrite. Am J Physiol Heart Circ Physiol 297:H1729–H1735. doi:10.1152/ajpheart.00484.2009

    PubMed  CAS  Google Scholar 

  117. Lambeth JD (2004) NOX enzymes and the biology of reactive oxygen. Nat Rev Immunol 4:181–189. doi:10.1038/nri1312

    PubMed  CAS  Google Scholar 

  118. Li H, Hemann C, Abdelghany TM, El-Mahdy MA, Zweier JL (2012) Characterization of the mechanism and magnitude of cytoglobin-mediated nitrite reduction and nitric oxide generation under anaerobic conditions. J Biol Chem 287:36623–36633. doi:10.1074/jbc.M112.342378

    PubMed  CAS  Google Scholar 

  119. Li H, Samouilov A, Liu X, Zweier JL (2004) Characterization of the effects of oxygen on xanthine oxidase-mediated nitric oxide formation. J Biol Chem 279:16939–16946. doi:10.1074/jbc.M314336200

    PubMed  CAS  Google Scholar 

  120. Li J, Umar S, Iorga A, Youn JY, Wang Y, Regitz-Zagrosek V, Cai H, Eghbali M (2012) Cardiac vulnerability to ischemia/reperfusion injury drastically increases in late pregnancy. Basic Res Cardiol 107:271. doi:10.1007/s00395-012-0271-7

    PubMed  Google Scholar 

  121. Li Q, Guo Y, Wu WJ, Ou Q, Zhu X, Tan W, Yuan F, Chen N, Dawn B, Luo L, O’Brien E, Bolli R (2011) Gene transfer as a strategy to achieve permanent cardioprotection I: rAAV-mediated gene therapy with inducible nitric oxide synthase limits infarct size 1 year later without adverse functional consequences. Basic Res Cardiol 106:1355–1366. doi:10.1007/s00395-011-0207-7

    PubMed  CAS  Google Scholar 

  122. Li Y, Huang TT, Carlson EJ, Melov S, Ursell PC, Olson JL, Noble LJ, Yoshimura MP, Berger C, Chan PH, Wallace DC, Epstein CJ (1995) Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase. Nat Genet 11:376–381. doi:10.1038/ng1295-376

    PubMed  CAS  Google Scholar 

  123. Lin J, Steenbergen C, Murphy E, Sun J (2009) Estrogen receptor-beta activation results in S-nitrosylation of proteins involved in cardioprotection. Circulation 120:245–254. doi:10.1161/CIRCULATIONAHA.109.868729

    PubMed  CAS  Google Scholar 

  124. Liu Y, Yang XM, Iliodromitis EK, Kremastinos DT, Dost T, Cohen MV, Downey JM (2008) Redox signaling at reperfusion is required for protection from ischemic preconditioning but not from a direct PKC activator. Basic Res Cardiol 103:54–59. doi:10.1007/s00395-007-0683-y

    PubMed  CAS  Google Scholar 

  125. Liu Y, Ytrehus K, Downey JM (1994) Evidence that translocation of protein kinase C is a key event during ischemic preconditioning of rabbit myocardium. J Mol Cell Cardiol 26:661–668. doi:10.1006/jmcc.1994.1078

    PubMed  CAS  Google Scholar 

  126. Loukogeorgakis SP, Williams R, Panagiotidou AT, Kolvekar SK, Donald A, Cole TJ, Yellon DM, Deanfield JE, MacAllister RJ (2007) Transient limb ischemia induces remote preconditioning and remote postconditioning in humans by a K(ATP)-channel dependent mechanism. Circulation 116:1386–1395. doi:10.1161/CIRCULATIONAHA.106.653782

    PubMed  CAS  Google Scholar 

  127. Luedike P, Hendgen-Cotta UB, Sobierajski J, Totzeck M, Reeh M, Dewor M, Lue H, Krisp C, Wolters D, Kelm M, Bernhagen J, Rassaf T (2012) Cardioprotection through S-nitros(yl)ation of macrophage migration inhibitory factor. Circulation 125:1880–1889. doi:10.1161/CIRCULATIONAHA.111.069104

    PubMed  CAS  Google Scholar 

  128. Manoury B, Montiel V, Balligand JL (2012) Nitric oxide synthase in post-ischaemic remodelling: new pathways and mechanisms. Cardiovasc Res 94:304–315. doi:10.1093/cvr/cvr360

    PubMed  CAS  Google Scholar 

  129. Marczin N, El-Habashi N, Hoare GS, Bundy RE, Yacoub M (2003) Antioxidants in myocardial ischemia-reperfusion injury: therapeutic potential and basic mechanisms. Arch Biochem Biophys 420:222–236. doi:10.1016/j.abb.2003.08.037

    PubMed  CAS  Google Scholar 

  130. Maroko PR, Libby P, Bloor CM, Sobel BE, Braunwald E (1972) Reduction by hyaluronidase of myocardial necrosis following coronary artery occlusion. Circulation 46:430–437. doi:10.1161/01.CIR.46.3.430

    PubMed  CAS  Google Scholar 

  131. Maroko PR, Libby P, Sobel BE, Bloor CM, Sybers HD, Shell WE, Covell JW, Braunwald E (1972) Effect of glucose-insulin-potassium infusion on myocardial infarction following experimental coronary artery occlusion. Circulation 45:1160–1175. doi:10.1161/01.CIR.45.6.1160

    PubMed  CAS  Google Scholar 

  132. Martin C, Schulz R, Post H, Boengler K, Kelm M, Kleinbongard P, Gres P, Skyschally A, Konietzka I, Heusch G (2007) Microdialysis-based analysis of interstitial NO in situ: NO synthase-independent NO formation during myocardial ischemia. Cardiovasc Res 74:46–55. doi:10.1016/j.cardiores.2006.12.020

    PubMed  CAS  Google Scholar 

  133. Martinez-Ruiz A, Araujo IM, Izquierdo-Alvarez A, Hernansanz-Agustin P, Lamas S, Serrador JM (2013) Specificity in S-nitrosylation: a short-range mechanism for NO signaling? Antioxid Redox Signal 19:1220–1235. doi:10.1089/ars.2012.5066

    PubMed  CAS  Google Scholar 

  134. Matsushima S, Ide T, Yamato M, Matsusaka H, Hattori F, Ikeuchi M, Kubota T, Sunagawa K, Hasegawa Y, Kurihara T, Oikawa S, Kinugawa S, Tsutsui H (2006) Overexpression of mitochondrial peroxiredoxin-3 prevents left ventricular remodeling and failure after myocardial infarction in mice. Circulation 113:1779–1786. doi:10.1161/CIRCULATIONAHA.105.582239

    PubMed  CAS  Google Scholar 

  135. Maulik N (2002) Redox signaling of angiogenesis. Antioxid Redox Signal 4:805–815. doi:10.1089/152308602760598963

    PubMed  CAS  Google Scholar 

  136. Monteiro HP, Gruia-Gray J, Peranovich TM, de Oliveira LC, Stern A (2000) Nitric oxide stimulates tyrosine phosphorylation of focal adhesion kinase, Src kinase, and mitogen-activated protein kinases in murine fibroblasts. Free Radic Biol Med 28:174–182. doi:10.1016/S0891-5849(99)00233-6

    PubMed  CAS  Google Scholar 

  137. Mozaffari MS, Baban B, Liu JY, Abebe W, Sullivan JC, El-Marakby A (2011) Mitochondrial complex I and NAD(P)H oxidase are major sources of exacerbated oxidative stress in pressure-overloaded ischemic-reperfused hearts. Basic Res Cardiol 106:287–297. doi:10.1007/s00395-011-0150-7

    PubMed  CAS  Google Scholar 

  138. Murphy E, Kohr M, Sun J, Nguyen T, Steenbergen C (2012) S-nitrosylation: a radical way to protect the heart. J Mol Cell Cardiol 52:568–577. doi:10.1016/j.yjmcc.2011.08.021

    PubMed  CAS  Google Scholar 

  139. Murphy MP (2012) Mitochondrial thiols in antioxidant protection and redox signaling: distinct roles for glutathionylation and other thiol modifications. Antioxid Redox Signal 16:476–495. doi:10.1089/ars.2011.4289

    PubMed  CAS  Google Scholar 

  140. Murry CE, Jennings RB, Reimer KA (1986) Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74:1124–1136. doi:10.1161/01.CIR.74.5.1124

    PubMed  CAS  Google Scholar 

  141. Na HS, Kim YI, Yoon YW, Han HC, Nahm SH, Hong SK (1996) Ventricular premature beat-driven intermittent restoration of coronary blood flow reduces the incidence of reperfusion-induced ventricular fibrillation in a cat model of regional ischemia. Am Heart J 132:78–83. doi:10.1016/S0002-8703(96)90393-2

    PubMed  CAS  Google Scholar 

  142. Nishino Y, Webb IG, Davidson SM, Ahmed AI, Clark JE, Jacquet S, Shah AM, Miura T, Yellon DM, Avkiran M, Marber MS (2008) Glycogen synthase kinase-3 inactivation is not required for ischemic preconditioning or postconditioning in the mouse. Circ Res 103:307–314. doi:10.1161/CIRCRESAHA.107.169953

    PubMed  CAS  Google Scholar 

  143. Nisimoto Y, Jackson HM, Ogawa H, Kawahara T, Lambeth JD (2010) Constitutive NADPH-dependent electron transferase activity of the Nox4 dehydrogenase domain. Biochemistry 49:2433–2442. doi:10.1021/bi9022285

    PubMed  CAS  Google Scholar 

  144. Nonn L, Williams RR, Erickson RP, Powis G (2003) The absence of mitochondrial thioredoxin 2 causes massive apoptosis, exencephaly, and early embryonic lethality in homozygous mice. Mol Cell Biol 23:916–922. doi:10.1128/MCB.23.3.916-922.2003

    PubMed  CAS  Google Scholar 

  145. Obame FN, Plin-Mercier C, Assaly R, Zini R, Dubois-Rande JL, Berdeaux A, Morin D (2008) Cardioprotective effect of morphine and a blocker of glycogen synthase kinase 3 beta, SB216763 [3-(2,4-dichlorophenyl)-4(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione], via inhibition of the mitochondrial permeability transition pore. J Pharmacol Exp Ther 326:252–258. doi:10.1124/jpet.108.138008

    PubMed  CAS  Google Scholar 

  146. Oldenburg O, Qin Q, Sharma AR, Cohen MV, Downey JM, Benoit JN (2002) Acetylcholine leads to free radical production dependent on K(ATP) channels, G(i) proteins, phosphatidylinositol 3-kinase and tyrosine kinase. Cardiovasc Res 55:544–552. doi:10.1016/S0008-6363(02)00332-2

    PubMed  CAS  Google Scholar 

  147. Oliveira CJ, Schindler F, Ventura AM, Morais MS, Arai RJ, Debbas V, Stern A, Monteiro HP (2003) Nitric oxide and cGMP activate the Ras-MAP kinase pathway-stimulating protein tyrosine phosphorylation in rabbit aortic endothelial cells. Free Radic Biol Med 35:381–396. doi:10.1016/S0891-5849(03)00311-3

    PubMed  CAS  Google Scholar 

  148. Ovize M, Baxter GF, Di Lisa F, Ferdinandy P, Garcia-Dorado D, Hausenloy DJ, Heusch G, Vinten-Johansen J, Yellon DM, Schulz R (2010) Postconditioning and protection from reperfusion injury: where do we stand? Position paper from the Working Group of Cellular Biology of the Heart of the European Society of Cardiology. Cardiovasc Res 87:406–423. doi:10.1093/cvr/cvq129

    PubMed  CAS  Google Scholar 

  149. Pagliaro P, Gattullo D, Rastaldo R, Losano G (2001) Ischemic preconditioning: from the first to the second window of protection. Life Sci 69:1–15. doi:10.1016/S0024-3205(01)01113-4

    PubMed  CAS  Google Scholar 

  150. Pagliaro P, Mancardi D, Rastaldo R, Penna C, Gattullo D, Miranda KM, Feelisch M, Wink DA, Kass DA, Paolocci N (2003) Nitroxyl affords thiol-sensitive myocardial protective effects akin to early preconditioning. Free Radic Biol Med 34:33–43. doi:10.1016/S0891-5849(02)01179-6

    PubMed  CAS  Google Scholar 

  151. Pagliaro P, Moro F, Tullio F, Perrelli MG, Penna C (2011) Cardioprotective pathways during reperfusion: focus on redox signaling and other modalities of cell signaling. Antioxid Redox Signal 14:833–850. doi:10.1089/ars.2010.3245

    PubMed  CAS  Google Scholar 

  152. Pagliaro P, Rastaldo R, Losano G, Gattullo D (2001) Mitochondrial ATP-sensitive channel opener does not induce vascular preconditioning, but potentiates the effect of a preconditioning ischemia on coronary reactive hyperemia in the anesthetized goat. Pflugers Arch 443:166–174. doi:10.1007/s004240100673

    PubMed  CAS  Google Scholar 

  153. Pagliaro P, Rastaldo R, Penna C, Mancardi D, Cappello S, Losano G (2004) Nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway is involved in ischemic postconditioning in the isolated rat heart. Circulation 110:III 136

    Google Scholar 

  154. Paillard M, Gomez L, Augeul L, Loufouat J, Lesnefsky EJ, Ovize M (2009) Postconditioning inhibits mPTP opening independent of oxidative phosphorylation and membrane potential. J Mol Cell Cardiol 46:902–909. doi:10.1016/j.yjmcc.2009.02.017

    PubMed  CAS  Google Scholar 

  155. Pain T, Yang XM, Critz SD, Yue Y, Nakano A, Liu GS, Heusch G, Cohen MV, Downey JM (2000) Opening of mitochondrial K(ATP) channels triggers the preconditioned state by generating free radicals. Circ Res 87:460–466. doi:10.1161/01.RES.87.6.460

    PubMed  CAS  Google Scholar 

  156. Pedersen CM, Schmidt MR, Barnes G, Botker HE, Kharbanda RK, Newby DE, Cruden NL (2011) Bradykinin does not mediate remote ischaemic preconditioning or ischaemia-reperfusion injury in vivo in man. Heart 97:1857–1861. doi:10.1136/heartjnl-2011-300323

    PubMed  CAS  Google Scholar 

  157. Penna C, Alloatti G, Cappello S, Gattullo D, Berta G, Mognetti B, Losano G, Pagliaro P (2005) Platelet-activating factor induces cardioprotection in isolated rat heart akin to ischemic preconditioning: role of phosphoinositide 3-kinase and protein kinase C activation. Am J Physiol Heart Circ Physiol 288:H2512–H2520. doi:10.1152/ajpheart.00599.2004

    PubMed  CAS  Google Scholar 

  158. Penna C, Cappello S, Mancardi D, Raimondo S, Rastaldo R, Gattullo D, Losano G, Pagliaro P (2006) Post-conditioning reduces infarct size in the isolated rat heart: role of coronary flow and pressure and the nitric oxide/cGMP pathway. Basic Res Cardiol 101:168–179. doi:10.1007/s00395-005-0543-6

    PubMed  CAS  Google Scholar 

  159. Penna C, Mancardi D, Raimondo S, Geuna S, Pagliaro P (2008) The paradigm of postconditioning to protect the heart. J Cell Mol Med 12:435–458. doi:10.1111/j.1582-4934.2007.00210.x

    PubMed  CAS  Google Scholar 

  160. Penna C, Mancardi D, Rastaldo R, Losano G, Pagliaro P (2007) Intermittent activation of bradykinin B2 receptors and mitochondrial KATP channels trigger cardiac postconditioning through redox signaling. Cardiovasc Res 75:168–177. doi:10.1016/j.cardiores.2007.03.001

    PubMed  CAS  Google Scholar 

  161. Penna C, Mancardi D, Rastaldo R, Pagliaro P (2009) Cardioprotection: a radical view Free radicals in pre and postconditioning. Biochim Biophys Acta 1787:781–793. doi:10.1016/j.bbabio.2009.02.008

    PubMed  CAS  Google Scholar 

  162. Penna C, Pagliaro P, Rastaldo R, Di Pancrazio F, Lippe G, Gattullo D, Mancardi D, Samaja M, Losano G, Mavelli I (2004) F0F1 ATP synthase activity is differently modulated by coronary reactive hyperemia before and after ischemic preconditioning in the goat. Am J Physiol Heart Circ Physiol 287:H2192–H2200. doi:10.1152/ajpheart.00327.2004

    PubMed  CAS  Google Scholar 

  163. Penna C, Perrelli M, Tullio F, Angotti C, Camporeale A, Poli V, Pagliaro P (2013) Diazoxide postconditioning induces mitochondrial protein S-Nitrosylation and a redox-sensitive mitochondrial phosphorylation/translocation of RISK elements: no role for SAFE. Basic Res Cardiol 108:371. doi:10.1007/s00395-013-0371-z

    PubMed  CAS  Google Scholar 

  164. Penna C, Perrelli MG, Pagliaro P (2013) Mitochondrial pathways, permeability transition pore, and redox signaling in cardioprotection: therapeutic implications. Antioxid Redox Signal 18:556–599. doi:10.1089/ars.2011.4459

    PubMed  CAS  Google Scholar 

  165. Penna C, Perrelli MG, Tullio F, Moro F, Parisella ML, Merlino A, Pagliaro P (2011) Post-ischemic early acidosis in cardiac postconditioning modifies the activity of antioxidant enzymes, reduces nitration, and favors protein S-nitrosylation. Pflugers Arch 462:219–233. doi:10.1007/s00424-011-0970-1

    PubMed  CAS  Google Scholar 

  166. Penna C, Raimondo S, Ronchi G, Rastaldo R, Mancardi D, Cappello S, Losano G, Geuna S, Pagliaro P (2008) Early homing of adult mesenchymal stem cells in normal and infarcted isolated beating hearts. J Cell Mol Med 12:507–521. doi:10.1111/j.1582-4934.2007.00121.x

    PubMed  Google Scholar 

  167. Penna C, Rastaldo R, Mancardi D, Raimondo S, Cappello S, Gattullo D, Losano G, Pagliaro P (2006) Post-conditioning induced cardioprotection requires signaling through a redox-sensitive mechanism, mitochondrial ATP-sensitive K+ channel and protein kinase C activation. Basic Res Cardiol 101:180–189. doi:10.1007/s00395-006-0584-5

    PubMed  CAS  Google Scholar 

  168. Perlman DH, Bauer SM, Ashrafian H, Bryan NS, Garcia-Saura MF, Lim CC, Fernandez BO, Infusini G, McComb ME, Costello CE, Feelisch M (2009) Mechanistic insights into nitrite-induced cardioprotection using an integrated metabolomic/proteomic approach. Circ Res 104:796–804. doi:10.1161/CIRCRESAHA.108.187005

    PubMed  CAS  Google Scholar 

  169. Pfeilschifter J, Eberhardt W, Beck KF (2001) Regulation of gene expression by nitric oxide. Pflugers Arch 442:479–486. doi:10.1007/s004240100586

    PubMed  CAS  Google Scholar 

  170. Pham FH, Sugden PH, Clerk A (2000) Regulation of protein kinase B and 4E-BP1 by oxidative stress in cardiac myocytes. Circ Res 86:1252–1258. doi:10.1161/01.RES.86.12.1252

    PubMed  CAS  Google Scholar 

  171. Philipp S, Yang XM, Cui L, Davis AM, Downey JM, Cohen MV (2006) Postconditioning protects rabbit hearts through a protein kinase C-adenosine A2b receptor cascade. Cardiovasc Res 70:308–314. doi:10.1016/j.cardiores.2006.02.014

    PubMed  CAS  Google Scholar 

  172. Piantadosi CA (2012) Regulation of mitochondrial processes by protein S-nitrosylation. Biochim Biophys Acta 1820:712–721. doi:10.1016/j.bbagen.2011.03.008

    PubMed  CAS  Google Scholar 

  173. Prime TA, Blaikie FH, Evans C, Nadtochiy SM, James AM, Dahm CC, Vitturi DA, Patel RP, Hiley CR, Abakumova I, Requejo R, Chouchani ET, Hurd TR, Garvey JF, Taylor CT, Brookes PS, Smith RA, Murphy MP (2009) A mitochondria-targeted S-nitrosothiol modulates respiration, nitrosates thiols, and protects against ischemia-reperfusion injury. Proc Natl Acad Sci USA 106:10764–10769. doi:10.1073/pnas.0903250106

    PubMed  CAS  Google Scholar 

  174. Przyklenk K, Bauer B, Ovize M, Kloner RA, Whittaker P (1993) Regional ischemic ‘preconditioning’ protects remote virgin myocardium from subsequent sustained coronary occlusion. Circulation 87:893–899. doi:10.1161/01.CIR.87.3.893

    PubMed  CAS  Google Scholar 

  175. Przyklenk K, Darling CE, Dickson EW, Whittaker P (2003) Cardioprotection ‘outside the box’–the evolving paradigm of remote preconditioning. Basic Res Cardiol 98:149–157. doi:10.1007/s00395-003-0406-y

    PubMed  Google Scholar 

  176. Quinlan CL, Costa AD, Costa CL, Pierre SV, Dos Santos P, Garlid KD (2008) Conditioning the heart induces formation of signalosomes that interact with mitochondria to open mitoKATP channels. Am J Physiol Heart Circ Physiol 295:H953–H961. doi:10.1152/ajpheart.00520.2008

    PubMed  CAS  Google Scholar 

  177. Radi R, Turrens JF, Chang LY, Bush KM, Crapo JD, Freeman BA (1991) Detection of catalase in rat heart mitochondria. J Biol Chem 266:22028–22034

    PubMed  CAS  Google Scholar 

  178. Rhee SG (1999) Redox signaling: hydrogen peroxide as intracellular messenger. Exp Mol Med 31:53–59. doi:10.1038/emm.1999.9

    PubMed  CAS  Google Scholar 

  179. Rhee SG, Bae YS, Lee SR, Kwon J (2000) Hydrogen peroxide: a key messenger that modulates protein phosphorylation through cysteine oxidation. Sci STKE 2000:pe1 doi:10.1126/stke.2000.53.pe1

  180. Rhee SG, Kang SW, Chang TS, Jeong W, Kim K (2001) Peroxiredoxin, a novel family of peroxidases. IUBMB Life 52:35–41. doi:10.1080/15216540252774748

    PubMed  CAS  Google Scholar 

  181. Rizzuto R, Pinton P, Carrington W, Fay FS, Fogarty KE, Lifshitz LM, Tuft RA, Pozzan T (1998) Close contacts with the endoplasmic reticulum as determinants of mitochondrial Ca2+ responses. Science 280:1763–1766. doi:10.1126/science.2805370.1763

    PubMed  CAS  Google Scholar 

  182. Rodriguez-Sinovas A, Boengler K, Cabestrero A, Gres P, Morente M, Ruiz-Meana M, Konietzka I, Miro E, Totzeck A, Heusch G, Schulz R, Garcia-Dorado D (2006) Translocation of connexin 43 to the inner mitochondrial membrane of cardiomyocytes through the heat shock protein 90-dependent TOM pathway and its importance for cardioprotection. Circ Res 99:93–101. doi:10.1161/01.RES.0000230315.56904.de

    PubMed  CAS  Google Scholar 

  183. Rodriguez-Sinovas A, Cabestrero A, Garcia del Blanco B, Inserte J, Garcia A, Garcia-Dorado D (2009) Intracoronary acid infusion as an alternative to ischemic postconditioning in pigs. Basic Res Cardiol 104:761–771. doi:10.1007/s00395-009-0032-4

    PubMed  CAS  Google Scholar 

  184. Rodriguez-Sinovas A, Sanchez JA, Gonzalez-Loyola A, Barba I, Morente M, Aguilar R, Agullo E, Miro-Casas E, Esquerda N, Ruiz-Meana M, Garcia-Dorado D (2010) Effects of substitution of Cx43 by Cx32 on myocardial energy metabolism, tolerance to ischaemia and preconditioning protection. J Physiol 588:1139–1151. doi:10.1113/jphysiol.2009.186577

    PubMed  CAS  Google Scholar 

  185. Salie R, Moolman JA, Lochner A (2012) The mechanism of beta-adrenergic preconditioning: roles for adenosine and ROS during triggering and mediation. Basic Res Cardiol 107:281. doi:10.1007/s00395-012-0281-5

    PubMed  Google Scholar 

  186. Salmeen A, Andersen JN, Myers MP, Meng TC, Hinks JA, Tonks NK, Barford D (2003) Redox regulation of protein tyrosine phosphatase 1B involves a sulphenyl-amide intermediate. Nature 423:769–773. doi:10.1038/nature01680

    PubMed  CAS  Google Scholar 

  187. Salvi M, Battaglia V, Brunati AM, La Rocca N, Tibaldi E, Pietrangeli P, Marcocci L, Mondovi B, Rossi CA, Toninello A (2007) Catalase takes part in rat liver mitochondria oxidative stress defense. J Biol Chem 282:24407–24415. doi:10.1074/jbc.M701589200

    PubMed  CAS  Google Scholar 

  188. Sanchez JA, Rodriguez-Sinovas A, Barba I, Miro-Casas E, Fernandez-Sanz C, Ruiz-Meana M, Alburquerque-Bejar JJ, Garcia-Dorado D (2013) Activation of RISK and SAFE pathways is not involved in the effects of Cx43 deficiency on tolerance to ischemia-reperfusion injury and preconditioning protection. Basic Res Cardiol 108:351. doi:10.1007/s00395-013-0351-3

    PubMed  Google Scholar 

  189. Santos CX, Anilkumar N, Zhang M, Brewer AC, Shah AM (2011) Redox signaling in cardiac myocytes. Free Radic Biol Med 50:777–793. doi:10.1016/j.freeradbiomed.2011.01.003

    PubMed  CAS  Google Scholar 

  190. Sarti P, Forte E, Mastronicola D, Giuffre A, Arese M (2012) Cytochrome c oxidase and nitric oxide in action: molecular mechanisms and pathophysiological implications. Biochim Biophys Acta 1817:610–619. doi:10.1016/j.bbabio.2011.09.002

    PubMed  CAS  Google Scholar 

  191. Schmidt MR, Smerup M, Konstantinov IE, Shimizu M, Li J, Cheung M, White PA, Kristiansen SB, Sorensen K, Dzavik V, Redington AN, Kharbanda RK (2007) Intermittent peripheral tissue ischemia during coronary ischemia reduces myocardial infarction through a KATP-dependent mechanism: first demonstration of remote ischemic perconditioning. Am J Physiol Heart Circ Physiol 292:H1883–H1890. doi:10.1152/ajpheart.00617.2006

    PubMed  CAS  Google Scholar 

  192. Schriner SE, Linford NJ, Martin GM, Treuting P, Ogburn CE, Emond M, Coskun PE, Ladiges W, Wolf N, Van Remmen H, Wallace DC, Rabinovitch PS (2005) Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 308:1909–1911. doi:10.1126/science.1106653

    PubMed  CAS  Google Scholar 

  193. Schulz R, Kelm M, Heusch G (2004) Nitric oxide in myocardial ischemia/reperfusion injury. Cardiovasc Res 61:402–413. doi:10.1016/j.cardiores.2003.09.019

    PubMed  CAS  Google Scholar 

  194. Shahid M, Tauseef M, Sharma KK, Fahim M (2008) Brief femoral artery ischaemia provides protection against myocardial ischaemia-reperfusion injury in rats: the possible mechanisms. Exp Physiol 93:954–968. doi:10.1113/expphysiol.2007.041442

    PubMed  CAS  Google Scholar 

  195. Shiomi T, Tsutsui H, Matsusaka H, Murakami K, Hayashidani S, Ikeuchi M, Wen J, Kubota T, Utsumi H, Takeshita A (2004) Overexpression of glutathione peroxidase prevents left ventricular remodeling and failure after myocardial infarction in mice. Circulation 109:544–549. doi:10.1161/01.CIR.0000109701.77059.E9

    PubMed  CAS  Google Scholar 

  196. Shiva S, Gladwin MT (2009) Nitrite mediates cytoprotection after ischemia/reperfusion by modulating mitochondrial function. Basic Res Cardiol 104:113–119. doi:10.1007/s00395-009-0009-3

    PubMed  CAS  Google Scholar 

  197. Shiva S, Sack MN, Greer JJ, Duranski M, Ringwood LA, Burwell L, Wang X, MacArthur PH, Shoja A, Raghavachari N, Calvert JW, Brookes PS, Lefer DJ, Gladwin MT (2007) Nitrite augments tolerance to ischemia/reperfusion injury via the modulation of mitochondrial electron transfer. J Exp Med 204:2089–2102. doi:10.1084/jem.20070198

    PubMed  CAS  Google Scholar 

  198. Simkhovich BZ, Przyklenk K, Hale SL, Patterson M, Kloner RA (1996) Direct evidence that ischemic preconditioning does not cause protein kinase C translocation in rabbit heart. Cardiovasc Res 32:1064–1070. doi:10.1016/S0008-6363(96)00181-2

    PubMed  CAS  Google Scholar 

  199. Skyschally A, Schulz R, Gres P, Korth HG, Heusch G (2003) Attenuation of ischemic preconditioning in pigs by scavenging of free oxyradicals with ascorbic acid. Am J Physiol Heart Circ Physiol 284:H698–H703. doi:10.1152/ajpheart.00693.2002

    PubMed  CAS  Google Scholar 

  200. Skyschally A, Van Caster P, Boengler K, Gres P, Musiolik J, Schilawa D, Schulz R, Heusch G (2009) Ischemic postconditioning in pigs: no causal role for RISK activation. Circ Res 104:15–18. doi:10.1161/CIRCRESAHA.108.186429

    PubMed  CAS  Google Scholar 

  201. Skyschally A, van Caster P, Iliodromitis EK, Schulz R, Kremastinos DT, Heusch G (2009) Ischemic postconditioning: experimental models and protocol algorithms. Basic Res Cardiol 104:469–483. doi:10.1007/s00395-009-0040-4

    PubMed  Google Scholar 

  202. Solenkova NV, Solodushko V, Cohen MV, Downey JM (2006) Endogenous adenosine protects preconditioned heart during early minutes of reperfusion by activating Akt. Am J Physiol Heart Circ Physiol 290:H441–H449. doi:10.1152/ajpheart.00589.2005

    PubMed  CAS  Google Scholar 

  203. Souza JM, Choi I, Chen Q, Weisse M, Daikhin E, Yudkoff M, Obin M, Ara J, Horwitz J, Ischiropoulos H (2000) Proteolytic degradation of tyrosine nitrated proteins. Arch Biochem Biophys 380:360–366. doi:10.1006/abbi.2000.1940

    PubMed  CAS  Google Scholar 

  204. St-Pierre J, Buckingham JA, Roebuck SJ, Brand MD (2002) Topology of superoxide production from different sites in the mitochondrial electron transport chain. J Biol Chem 277:44784–44790. doi:10.1074/jbc.M207217200

    PubMed  CAS  Google Scholar 

  205. Stamler JS, Toone EJ (2002) The decomposition of thionitrites. Curr Opin Chem Biol 6:779–785. doi:10.1016/S1367-5931(02)00383-6

    PubMed  CAS  Google Scholar 

  206. Steinhubl SR (2008) Why have antioxidants failed in clinical trials? Am J Cardiol 101:14D–19D. doi:10.1016/j.amjcard.2008.02.003

    PubMed  CAS  Google Scholar 

  207. Suleman N, Somers S, Smith R, Opie LH, Lecour SC (2008) Dual activation of STAT-3 and Akt is required during the trigger phase of ischaemic preconditioning. Cardiovasc Res 79:127–133. doi:10.1093/cvr/cvn067

    PubMed  CAS  Google Scholar 

  208. Sun J (2007) Protein S-nitrosylation: a role of nitric oxide signaling in cardiac ischemic preconditioning. Sheng Li Xue Bao 59:544–552

    PubMed  CAS  Google Scholar 

  209. Sun J, Kohr MJ, Nguyen T, Aponte AM, Connelly PS, Esfahani SG, Gucek M, Daniels MP, Steenbergen C, Murphy E (2012) Disruption of caveolae blocks ischemic preconditioning-mediated S-nitrosylation of mitochondrial proteins. Antioxid Redox Signal 16:45–56. doi:10.1089/ars.2010.3844

    PubMed  CAS  Google Scholar 

  210. Sun J, Murphy E (2010) Protein S-nitrosylation and cardioprotection. Circ Res 106:285–296. doi:10.1161/CIRCRESAHA.109.209452

    PubMed  CAS  Google Scholar 

  211. Szijarto A, Czigany Z, Turoczi Z, Harsanyi L (2012) Remote ischemic perconditioning–a simple, low-risk method to decrease ischemic reperfusion injury: models, protocols and mechanistic background. A review. J Surg Res 178:797–806. doi:10.1016/j.jss.2012.06.067

    PubMed  Google Scholar 

  212. Takakura K, Beckman JS, MacMillan-Crow LA, Crow JP (1999) Rapid and irreversible inactivation of protein tyrosine phosphatases PTP1B, CD45, and LAR by peroxynitrite. Arch Biochem Biophys 369:197–207. doi:10.1006/abbi.1999.1374

    PubMed  CAS  Google Scholar 

  213. Tomasian D, Keaney JF, Vita JA (2000) Antioxidants and the bioactivity of endothelium-derived nitric oxide. Cardiovasc Res 47:426–435. doi:10.1016/S0008-6363(00)00103-6

    PubMed  CAS  Google Scholar 

  214. Totzeck M, Hendgen-Cotta UB, Luedike P, Berenbrink M, Klare JP, Steinhoff HJ, Semmler D, Shiva S, Williams D, Kipar A, Gladwin MT, Schrader J, Kelm M, Cossins AR, Rassaf T (2012) Nitrite regulates hypoxic vasodilation via myoglobin-dependent nitric oxide generation. Circulation 126:325–334. doi:10.1161/CIRCULATIONAHA.111.087155

    PubMed  CAS  Google Scholar 

  215. Touyz RM (2004) Reactive oxygen species, vascular oxidative stress, and redox signaling in hypertension: what is the clinical significance? Hypertension 44:248–252. doi:10.1161/01.HYP.0000138070.47616.9d

    PubMed  CAS  Google Scholar 

  216. Tritto I, Ambrosio G (2001) Role of oxidants in the signaling pathway of preconditioning. Antioxid Redox Signal 3:3–10. doi:10.1089/152308601750100425

    PubMed  CAS  Google Scholar 

  217. Tritto I, D’Andrea D, Eramo N, Scognamiglio A, De Simone C, Violante A, Esposito A, Chiariello M, Ambrosio G (1997) Oxygen radicals can induce preconditioning in rabbit hearts. Circ Res 80:743–748. doi:10.1161/01.RES.80.5.743

    PubMed  CAS  Google Scholar 

  218. Tsang A, Hausenloy DJ, Mocanu MM, Yellon DM (2004) Postconditioning: a form of “modified reperfusion” protects the myocardium by activating the phosphatidylinositol 3-kinase-Akt pathway. Circ Res 95:230–232. doi:10.1161/01.RES.0000138303.76488.fe

    PubMed  CAS  Google Scholar 

  219. Tsutsumi YM, Yokoyama T, Horikawa Y, Roth DM, Patel HH (2007) Reactive oxygen species trigger ischemic and pharmacological postconditioning: in vivo and in vitro characterization. Life Sci 81:1223–1227. doi:10.1016/j.lfs.2007.08.031

    PubMed  CAS  Google Scholar 

  220. Ushio-Fukai M (2009) Compartmentalization of redox signaling through NADPH oxidase-derived ROS. Antioxid Redox Signal 11:1289–1299. doi:10.1089/ARS.2008.2333

    PubMed  CAS  Google Scholar 

  221. Vadseth C, Souza JM, Thomson L, Seagraves A, Nagaswami C, Scheiner T, Torbet J, Vilaire G, Bennett JS, Murciano JC, Muzykantov V, Penn MS, Hazen SL, Weisel JW, Ischiropoulos H (2004) Pro-thrombotic state induced by post-translational modification of fibrinogen by reactive nitrogen species. J Biol Chem 279:8820–8826. doi:10.1074/jbc.M306101200

    PubMed  CAS  Google Scholar 

  222. Valentim L, Laurence KM, Townsend PA, Carroll CJ, Soond S, Scarabelli TM, Knight RA, Latchman DS, Stephanou A (2006) Urocortin inhibits Beclin1-mediated autophagic cell death in cardiac myocytes exposed to ischaemia/reperfusion injury. J Mol Cell Cardiol 40:846–852. doi:10.1016/j.yjmcc.2006.03.428

    PubMed  CAS  Google Scholar 

  223. van der Vliet A (2008) NADPH oxidases in lung biology and pathology: host defense enzymes, and more. Free Radic Biol Med 44:938–955. doi:10.1016/j.freeradbiomed.2007.11.016

    PubMed  Google Scholar 

  224. van Faassen EE, Bahrami S, Feelisch M, Hogg N, Kelm M, Kim-Shapiro DB, Kozlov AV, Li H, Lundberg JO, Mason R, Nohl H, Rassaf T, Samouilov A, Slama-Schwok A, Shiva S, Vanin AF, Weitzberg E, Zweier J, Gladwin MT (2009) Nitrite as regulator of hypoxic signaling in mammalian physiology. Med Res Rev 29:683–741. doi:10.1002/med.20151

    PubMed  Google Scholar 

  225. Vanden Hoek TL, Becker LB, Shao Z, Li C, Schumacker PT (1998) Reactive oxygen species released from mitochondria during brief hypoxia induce preconditioning in cardiomyocytes. J Biol Chem 273:18092–18098. doi:10.1074/jbc.273.29.18092

    PubMed  CAS  Google Scholar 

  226. Vernon PJ, Tang D (2013) Eat-me: autophagy, phagocytosis, and reactive oxygen species signaling. Antioxid Redox Signal 18:677–691. doi:10.1089/ars.2012.4810

    PubMed  CAS  Google Scholar 

  227. Vivekananthan DP, Penn MS, Sapp SK, Hsu A, Topol EJ (2003) Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials. Lancet 361:2017–2023. doi:10.1016/S0140-6736(03)13637-9

    PubMed  CAS  Google Scholar 

  228. Webb A, Bond R, McLean P, Uppal R, Benjamin N, Ahluwalia A (2004) Reduction of nitrite to nitric oxide during ischemia protects against myocardial ischemia-reperfusion damage. Proc Natl Acad Sci USA 101:13683–13688. doi:10.1073/pnas.0402927101

    PubMed  CAS  Google Scholar 

  229. Williams-Pritchard G, Knight M, Hoe LS, Headrick JP, Peart JN (2011) Essential role of EGFR in cardioprotection and signaling responses to A1 adenosine receptors and ischemic preconditioning. Am J Physiol Heart Circ Physiol 300:H2161–H2168. doi:10.1152/ajpheart.00639.2010

    PubMed  CAS  Google Scholar 

  230. Wink DA, Mitchell JB (1998) Chemical biology of nitric oxide: insights into regulatory, cytotoxic, and cytoprotective mechanisms of nitric oxide. Free Radic Biol Med 25:434–456. doi:10.1016/S0891-5849(98)00092-6

    PubMed  CAS  Google Scholar 

  231. Wolin MS (2000) Interactions of oxidants with vascular signaling systems. Arterioscler Thromb Vasc Biol 20:1430–1442. doi:10.1161/01.ATV.20.6.1430

    PubMed  CAS  Google Scholar 

  232. Yao Z, Tong J, Tan X, Li C, Shao Z, Kim WC, vanden Hoek TL, Becker LB, Head CA, Schumacker PT (1999) Role of reactive oxygen species in acetylcholine-induced preconditioning in cardiomyocytes. Am J Physiol 277:H2504–H2509

    PubMed  CAS  Google Scholar 

  233. Yellon DM, Downey JM (2003) Preconditioning the myocardium: from cellular physiology to clinical cardiology. Physiol Rev 83:1113–1151. doi:10.1152/physrev.00009.2003

    PubMed  CAS  Google Scholar 

  234. Yellon DM, Hausenloy DJ (2007) Myocardial reperfusion injury. N Engl J Med 357:1121–1135. doi:10.1056/NEJMra071667

    PubMed  CAS  Google Scholar 

  235. Yue Y, Qin Q, Cohen MV, Downey JM, Critz SD (2002) The relative order of mK(ATP) channels, free radicals and p38 MAPK in preconditioning’s protective pathway in rat heart. Cardiovasc Res 55:681–689. doi:10.1016/S0008-6363(02)00452-2

    PubMed  CAS  Google Scholar 

  236. Zhang M, Brewer AC, Schroder K, Santos CX, Grieve DJ, Wang M, Anilkumar N, Yu B, Dong X, Walker SJ, Brandes RP, Shah AM (2010) NADPH oxidase-4 mediates protection against chronic load-induced stress in mouse hearts by enhancing angiogenesis. Proc Natl Acad Sci USA 107:18121–18126. doi:10.1073/pnas.1009700107

    PubMed  CAS  Google Scholar 

  237. Zhang M, Perino A, Ghigo A, Hirsch E, Shah AM (2013) NADPH oxidases in heart failure: poachers or gamekeepers? Antioxid Redox Signal 18:1024–1041. doi:10.1089/ars.2012.4550

    PubMed  CAS  Google Scholar 

  238. Zhao F, Ilbert M, Varadan R, Cremers CM, Hoyos B, Acin-Perez R, Vinogradov V, Cowburn D, Jakob U, Hammerling U (2011) Are zinc-finger domains of protein kinase C dynamic structures that unfold by lipid or redox activation? Antioxid Redox Signal 14:757–766. doi:10.1089/ars.2010.3773

    PubMed  CAS  Google Scholar 

  239. Zhao JL, Yang YJ, Pei WD, Sun YH, You SJ, Gao RL (2009) Remote periconditioning reduces myocardial no-reflow by the activation of K ATP channel via inhibition of Rho-kinase. Int J Cardiol 133:179–184. doi:10.1016/j.ijcard.2007.12.024

    PubMed  Google Scholar 

  240. Zhao ZQ, Corvera JS, Halkos ME, Kerendi F, Wang NP, Guyton RA, Vinten-Johansen J (2003) Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning. Am J Physiol Heart Circ Physiol 285:H579–H588. doi:10.1152/ajpheart.01064.2002

    PubMed  CAS  Google Scholar 

  241. Zielonka J, Sikora A, Joseph J, Kalyanaraman B (2010) Peroxynitrite is the major species formed from different flux ratios of co-generated nitric oxide and superoxide: direct reaction with boronate-based fluorescent probe. J Biol Chem 285:14210–14216. doi:10.1074/jbc.M110.110080

    PubMed  CAS  Google Scholar 

  242. Zweier JL, Chen CA, Druhan LJ (2011) S-glutathionylation reshapes our understanding of endothelial nitric oxide synthase uncoupling and nitric oxide/reactive oxygen species-mediated signaling. Antioxid Redox Signal 14:1769–1775. doi:10.1089/ars.2011.3904

    PubMed  CAS  Google Scholar 

  243. Zweier JL, Li H, Samouilov A, Liu X (2010) Mechanisms of nitrite reduction to nitric oxide in the heart and vessel wall. Nitric Oxide 22:83–90. doi:10.1016/j.niox.2009.12.004

    PubMed  CAS  Google Scholar 

  244. Zweier JL, Samouilov A, Kuppusamy P (1999) Non-enzymatic nitric oxide synthesis in biological systems. Biochim Biophys Acta 1411:250–262. doi:10.1016/S0005-2728(99)00018-3

    PubMed  CAS  Google Scholar 

  245. Zweier JL, Wang P, Samouilov A, Kuppusamy P (1995) Enzyme-independent formation of nitric oxide in biological tissues. Nat Med 1:804–809. doi:10.1038/nm0895-804

    PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Prof. Donatella Gattullo and Dr. Saveria Femminò for the invaluable support.

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  1. Dipartimento di Scienze Cliniche e Biologiche, Università di Torino, Ospedale S. Luigi, Regione Gonzole,10, 10043, Orbassano (TO), Italy

    Francesca Tullio, Carmelina Angotti, Maria-Giulia Perrelli, Claudia Penna & Pasquale Pagliaro

  2. Istituto Nazionale Ricerche Cardiovascolari (INRC), Bologna, Italy

    Francesca Tullio, Carmelina Angotti, Maria-Giulia Perrelli, Claudia Penna & Pasquale Pagliaro

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Tullio, F., Angotti, C., Perrelli, MG. et al. Redox balance and cardioprotection. Basic Res Cardiol 108, 392 (2013). https://doi.org/10.1007/s00395-013-0392-7

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