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RISK and SAFE signaling pathway interactions in remote limb ischemic perconditioning in combination with local ischemic postconditioning

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Abstract

Local ischemic postconditioning (IPost) and remote ischemic perconditioning (RIPer) are promising methods to decrease ischemia–reperfusion (I/R) injury. We tested whether the use of the two procedures in combination led to an improvement in cardioprotection through a higher activation of survival signaling pathways. Rats exposed to myocardial I/R were allocated to one of the following four groups: Control, no intervention at myocardial reperfusion; IPost, three cycles of 10-s coronary artery occlusion followed by 10-s reperfusion applied at the onset of myocardial reperfusion; RIPer, 10-min limb ischemia followed by 10-min reperfusion initiated 20 min after coronary artery occlusion; IPost+RIPer, IPost and RIPer in combination. Infarct size was significantly reduced in both IPost and RIPer (34.25 ± 3.36 and 24.69 ± 6.02%, respectively) groups compared to Control (54.93 ± 6.46%, both p < 0.05). IPost+RIPer (infarct size = 18.04 ± 4.86%) was significantly more cardioprotective than IPost alone (p < 0.05). RISK pathway (Akt, ERK1/2, and GSK-3β) activation was enhanced in IPost, RIPer, and IPost+RIPer groups compared to Control. IPost+RIPer did not enhance RISK pathway activation as compared to IPost alone, but instead increased phospho-STAT-3 levels, highlighting the crucial role of the SAFE pathway. In IPost+RIPer, a SAFE inhibitor (AG490) abolished cardioprotection and blocked both Akt and GSK-3β phosphorylations, whereas RISK inhibitors (wortmannin or U0126) abolished cardioprotection and blocked STAT-3 phosphorylation. In our experimental model, the combination of IPost and RIPer improved cardioprotection through the recruitment of the SAFE pathway. Our findings also indicate that cross talk exists between the RISK and SAFE pathways.

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References

  1. Ali ZA, Callaghan CJ, Lim E, Ali AA, Nouraei SA, Akthar AM, Boyle JR, Varty K, Kharbanda RK, Dutka DP, Gaunt ME (2007) Remote ischemic preconditioning reduces myocardial and renal injury after elective abdominal aortic aneurysm repair: a randomized controlled trial. Circulation 116:I98–I105. doi:10.1161/circulationaha.106.679167

    Article  PubMed  Google Scholar 

  2. Andreka G, Vertesaljai M, Szantho G, Font G, Piroth Z, Fontos G, Juhasz ED, Szekely L, Szelid Z, Turner MS, Ashrafian H, Frenneaux MP, Andreka P (2007) Remote ischaemic postconditioning protects the heart during acute myocardial infarction in pigs. Heart 93:749–752. doi:10.1136/hrt.2006.114504

    Article  PubMed  Google Scholar 

  3. Boengler K, Buechert A, Heinen Y, Roeskes C, Hilfiker-Kleiner D, Heusch G, Schulz R (2008) Cardioprotection by ischemic postconditioning is lost in aged and STAT3-deficient mice. Circ Res 102:131–135. doi:10.1161/CIRCRESAHA.107.164699

    Article  PubMed  CAS  Google Scholar 

  4. Boengler K, Heusch G, Schulz R Mitochondria in Postconditioning (2011). Antioxid Redox Signal 14:863-881 doi: 10.1089/ars.2010.3309

  5. Boengler K, Hilfiker-Kleiner D, Drexler H, Heusch G, Schulz R (2008) The myocardial JAK/STAT pathway: from protection to failure. Pharmacol Ther 120:172–185. doi:10.1016/j.pharmthera.2008.08.002

    Article  PubMed  CAS  Google Scholar 

  6. Boengler K, Hilfiker-Kleiner D, Heusch G, Schulz R (2010) Inhibition of permeability transition pore opening by mitochondrial STAT3 and its role in myocardial ischemia/reperfusion. Basic Res Cardiol 105:771–785. doi:10.1007/s00395-010-0124-1

    Article  PubMed  CAS  Google Scholar 

  7. Botker HE, Kharbanda R, Schmidt MR, Bottcher M, Kaltoft AK, Terkelsen CJ, Munk K, Andersen NH, Hansen TM, Trautner S, Lassen JF, Christiansen EH, Krusell LR, Kristensen SD, Thuesen L, Nielsen SS, Rehling M, Sorensen HT, Redington AN, Nielsen TT (2010) Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial. Lancet 375:727–734. doi:10.1016/S0140-6736(09)62001-8

    Article  PubMed  Google Scholar 

  8. Breivik L, Helgeland E, Aarnes EK, Mrdalj J, Jonassen AK (2011) Remote postconditioning by humoral factors in effluent from ischemic preconditioned rat hearts is mediated via PI3 K/Akt-dependent cell-survival signaling at reperfusion. Basic Res Cardiol 106:135–145. doi:10.1007/s00395-010-0133-0

    Article  PubMed  CAS  Google Scholar 

  9. Dickson EW, Reinhardt CP, Renzi FP, Becker RC, Porcaro WA, Heard SO (1999) Ischemic preconditioning may be transferable via whole blood transfusion: preliminary evidence. J Thromb Thrombolysis 8:123–129

    Article  PubMed  CAS  Google Scholar 

  10. Dong JH, Liu YX, Ji ES, He RR (2004) Limb ischemic preconditioning reduces infarct size following myocardial ischemia-reperfusion in rats. Sheng Li Xue Bao 56:41–46

    PubMed  Google Scholar 

  11. Ghaboura N, Tamareille S, Ducluzeau PH, Grimaud L, Loufrani L, Croue A, Tourmen Y, Henrion D, Furber A, Prunier F (2011) Diabetes mellitus abrogates erythropoietin-induced cardioprotection against ischemic-reperfusion injury by alteration of the RISK/GSK-3beta signaling. Basic Res Cardiol 106:147–162. doi:10.1007/s00395-010-0130-3

    Article  PubMed  CAS  Google Scholar 

  12. Goodman MD, Koch SE, Fuller-Bicer GA, Butler KL (2008) Regulating RISK: a role for JAK-STAT signaling in postconditioning? Am J Physiol Heart Circ Physiol 295:H1649–H1656. doi:10.1152/ajpheart.00692.2008

    Article  PubMed  CAS  Google Scholar 

  13. Gritsopoulos G, Iliodromitis EK, Zoga A, Farmakis D, Demerouti E, Papalois A, Paraskevaidis IA, Kremastinos DT (2009) Remote postconditioning is more potent than classic postconditioning in reducing the infarct size in anesthetized rabbits. Cardiovasc Drugs Ther 23:193–198. doi:10.1007/s10557-009-6168-5

    Article  PubMed  CAS  Google Scholar 

  14. Gross ER, Hsu AK, Gross GJ (2006) The JAK/STAT pathway is essential for opioid-induced cardioprotection: JAK2 as a mediator of STAT3, Akt, and GSK-3 beta. Am J Physiol Heart Circ Physiol 291:H827–H834. doi:10.1152/ajpheart.00003.2006

    Article  PubMed  CAS  Google Scholar 

  15. Hausenloy DJ, Baxter G, Bell R, Botker HE, Davidson SM, Downey J, Heusch G, Kitakaze M, Lecour S, Mentzer R, Mocanu MM, Ovize M, Schulz R, Shannon R, Walker M, Walkinshaw G, Yellon DM (2010) Translating novel strategies for cardioprotection: the Hatter Workshop Recommendations. Basic Res Cardiol 105:677–686. doi:10.1007/s00395-010-0121-4

    Article  PubMed  Google Scholar 

  16. 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

    Article  PubMed  CAS  Google Scholar 

  17. Hausenloy DJ, Mwamure PK, Venugopal V, Harris J, Barnard M, Grundy E, Ashley E, Vichare S, Di Salvo C, Kolvekar S, Hayward M, Keogh B, MacAllister RJ, Yellon DM (2007) Effect of remote ischaemic preconditioning on myocardial injury in patients undergoing coronary artery bypass graft surgery: a randomised controlled trial. Lancet 370:575–579. doi:10.1016/S0140-6736(07)61296-3

    Article  PubMed  Google Scholar 

  18. Hausenloy DJ, Tsang A, Yellon DM (2005) The reperfusion injury salvage kinase pathway: a common target for both ischemic preconditioning and postconditioning. Trends Cardiovasc Med 15:69–75. doi:10.1016/j.tcm.2005.03.001

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  20. Hausenloy DJ, Yellon DM (2006) Survival kinases in ischemic preconditioning and postconditioning. Cardiovasc Res 70:240–253. doi:10.1016/j.cardiores.2006.01.017

    Article  PubMed  CAS  Google Scholar 

  21. Heidbreder M, Naumann A, Tempel K, Dominiak P, Dendorfer A (2008) Remote vs. ischaemic preconditioning: the differential role of mitogen-activated protein kinase pathways. Cardiovasc Res 78:108–115. doi:10.1093/cvr/cvm114

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  23. Heusch G, Boengler K, Schulz R (2008) Cardioprotection: nitric oxide, protein kinases, and mitochondria. Circulation 118:1915–1919. doi:10.1161/CIRCULATIONAHA.108.805242

    Article  PubMed  Google Scholar 

  24. 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

    Article  PubMed  Google Scholar 

  25. Heusch G, Schulz R (2002) Remote preconditioning. J Mol Cell Cardiol 34:1279–1281. doi:10.1006/jmcc.2002.2093

    Article  PubMed  CAS  Google Scholar 

  26. Hoole SP, Heck PM, Sharples L, Khan SN, Duehmke R, Densem CG, Clarke SC, Shapiro LM, Schofield PM, O’Sullivan M, Dutka DP (2009) Cardiac Remote Ischemic Preconditioning in Coronary Stenting (CRISP Stent) Study: a prospective, randomized control trial. Circulation 119:820–827. doi:10.1161/CIRCULATIONAHA.108.809723

    Article  PubMed  Google Scholar 

  27. Juhaszova M, Zorov DB, Kim SH, Pepe S, Fu Q, Fishbein KW, Ziman BD, Wang S, Ytrehus K, Antos CL, Olson EN, Sollott SJ (2004) Glycogen synthase kinase-3beta mediates convergence of protection signaling to inhibit the mitochondrial permeability transition pore. J Clin Invest 113:1535–1549. doi:10.1172/JCI19906

    PubMed  CAS  Google Scholar 

  28. Kaur S, Jaggi AS, Singh N (2009) Molecular aspects of ischaemic postconditioning. Fundam Clin Pharmacol 23:521–536. doi:10.1111/j.1472-8206.2009.00733.x

    Article  PubMed  CAS  Google Scholar 

  29. Kelly RF, Lamont KT, Somers S, Hacking D, Lacerda L, Thomas P, Opie LH, Lecour S (2010) Ethanolamine is a novel STAT-3 dependent cardioprotective agent. Basic Res Cardiol 105:763–770. doi:10.1007/s00395-010-0125-0

    Article  PubMed  CAS  Google Scholar 

  30. Kerendi F, Kin H, Halkos ME, Jiang R, Zatta AJ, Zhao ZQ, Guyton RA, Vinten-Johansen J (2005) Remote postconditioning. Brief renal ischemia and reperfusion applied before coronary artery reperfusion reduces myocardial infarct size via endogenous activation of adenosine receptors. Basic Res Cardiol 100:404–412. doi:10.1007/s00395-005-0539-2

    Article  PubMed  CAS  Google Scholar 

  31. Kharbanda RK (2010) Cardiac conditioning: a review of evolving strategies to reduce ischaemia-reperfusion injury. Heart 96:1179–1186. doi:10.1136/hrt.2009.179101

    Article  PubMed  CAS  Google Scholar 

  32. Kin H, Wang NP, Mykytenko J, Reeves J, Deneve J, Jiang R, Zatta AJ, Guyton RA, Vinten-Johansen J, Zhao ZQ (2008) Inhibition of myocardial apoptosis by postconditioning is associated with attenuation of oxidative stress-mediated nuclear factor-kappa B translocation and TNF alpha release. Shock 29:761–768. doi:10.1097/SHK.0b013e31815cfd5a

    PubMed  CAS  Google Scholar 

  33. 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

    Article  PubMed  CAS  Google Scholar 

  34. Lacerda L, McCarthy J, Mungly SF, Lynn EG, Sack MN, Opie LH, Lecour S (2010) TNFalpha protects cardiac mitochondria independently of its cell surface receptors. Basic Res Cardiol 105:751–762. doi:10.1007/s00395-010-0113-4

    Article  PubMed  CAS  Google Scholar 

  35. Lacerda L, Somers S, Opie LH, Lecour S (2009) Ischaemic postconditioning protects against reperfusion injury via the SAFE pathway. Cardiovasc Res 84:201–208. doi:10.1093/cvr/cvp274

    Article  PubMed  CAS  Google Scholar 

  36. Lecour S (2009) Activation of the protective Survivor Activating Factor Enhancement (SAFE) pathway against reperfusion injury: Does it go beyond the RISK pathway? J Mol Cell Cardiol 47:32–40. doi:10.1016/j.yjmcc.2009.03.019

    Article  PubMed  CAS  Google Scholar 

  37. Lecour S (2009) Multiple protective pathways against reperfusion injury: a SAFE path without Aktion? J Mol Cell Cardiol 46:607–609. doi:10.1016/j.yjmcc.2009.01.003

    Article  PubMed  CAS  Google Scholar 

  38. Li CM, Zhang XH, Ma XJ, Luo M (2006) Limb ischemic postconditioning protects myocardium from ischemia-reperfusion injury. Scand Cardiovasc J 40:312–317. doi:10.1080/14017430600925292

    Article  PubMed  Google Scholar 

  39. Lim SY, Yellon DM, Hausenloy DJ (2010) The neural and humoral pathways in remote limb ischemic preconditioning. Basic Res Cardiol 105:651–655. doi:10.1007/s00395-010-0099-y

    Article  PubMed  Google Scholar 

  40. 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

    Article  PubMed  CAS  Google Scholar 

  41. Murray CJ, Lopez AD (1997) Alternative projections of mortality and disability by cause 1990–2020: Global Burden of Disease Study. Lancet 349:1498–1504. doi:10.1016/S0140-6736(96)07492-2

    Article  PubMed  CAS  Google Scholar 

  42. 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

    Article  PubMed  CAS  Google Scholar 

  43. Oxman T, Arad M, Klein R, Avazov N, Rabinowitz B (1997) Limb ischemia preconditions the heart against reperfusion tachyarrhythmia. Am J Physiol 273:H1707–H1712

    PubMed  CAS  Google Scholar 

  44. Peart JN, Gross ER, Reichelt ME, Hsu A, Headrick JP, Gross GJ (2008) Activation of kappa-opioid receptors at reperfusion affords cardioprotection in both rat and mouse hearts. Basic Res Cardiol 103:454–463. doi:10.1007/s00395-008-0726-z

    Article  PubMed  CAS  Google Scholar 

  45. Pell TJ, Baxter GF, Yellon DM, Drew GM (1998) Renal ischemia preconditions myocardium: role of adenosine receptors and ATP-sensitive potassium channels. Am J Physiol 275:H1542–H1547

    PubMed  CAS  Google Scholar 

  46. Piper HM, Garcia-Dorado D, Ovize M (1998) A fresh look at reperfusion injury. Cardiovasc Res 38:291–300

    Article  PubMed  CAS  Google Scholar 

  47. Rentoukas I, Giannopoulos G, Kaoukis A, Kossyvakis C, Raisakis K, Driva M, Panagopoulou V, Tsarouchas K, Vavetsi S, Pyrgakis V, Deftereos S (2010) Cardioprotective role of remote ischemic periconditioning in primary percutaneous coronary intervention: enhancement by opioid action. JACC Cardiovasc Interv 3:49–55. doi:10.1016/j.jcin.2009.10.015

    Article  PubMed  Google Scholar 

  48. Saxena P, Newman MA, Shehatha JS, Redington AN, Konstantinov IE (2010) Remote ischemic conditioning: evolution of the concept, mechanisms, and clinical application. J Card Surg 25:127–134. doi:10.1111/j.1540-8191.2009.00820.x

    Article  PubMed  Google Scholar 

  49. 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

    Article  PubMed  CAS  Google Scholar 

  50. Schwartz LM, Lagranha CJ (2006) Ischemic postconditioning during reperfusion activates Akt and ERK without protecting against lethal myocardial ischemia-reperfusion injury in pigs. Am J Physiol Heart Circ Physiol 290:H1011–H1018. doi:10.1152/ajpheart.00864.2005

    Article  PubMed  CAS  Google Scholar 

  51. 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

    Article  PubMed  CAS  Google Scholar 

  52. 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

    Article  PubMed  Google Scholar 

  53. 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

    Article  PubMed  CAS  Google Scholar 

  54. Tamareille S, Ghaboura N, Treguer F, Khachman D, Croue A, Henrion D, Furber A, Prunier F (2009) Myocardial reperfusion injury management: erythropoietin compared with postconditioning. Am J Physiol Heart Circ Physiol 297:H2035–H2043. doi:10.1152/ajpheart.00472.2009

    Article  PubMed  CAS  Google Scholar 

  55. Thielmann M, Kottenberg E, Boengler K, Raffelsieper C, Neuhaeuser M, Peters J, Jakob H, Heusch G (2010) Remote ischemic preconditioning reduces myocardial injury after coronary artery bypass surgery with crystalloid cardioplegic arrest. Basic Res Cardiol 105:657–664. doi:10.1007/s00395-010-0104-5

    Article  PubMed  CAS  Google Scholar 

  56. 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

    Article  PubMed  CAS  Google Scholar 

  57. Weinbrenner C, Schulze F, Sarvary L, Strasser RH (2004) Remote preconditioning by infrarenal aortic occlusion is operative via delta1-opioid receptors and free radicals in vivo in the rat heart. Cardiovasc Res 61:591–599. doi:10.1016/j.cardiores.2003.10.008

    Article  PubMed  CAS  Google Scholar 

  58. Wolfrum S, Schneider K, Heidbreder M, Nienstedt J, Dominiak P, Dendorfer A (2002) Remote preconditioning protects the heart by activating myocardial PKCepsilon-isoform. Cardiovasc Res 55:583–589

    Article  PubMed  CAS  Google Scholar 

  59. Xin P, Zhu W, Li J, Ma S, Wang L, Liu M, Wei M, Redington AN (2010) Combined local ischemic postconditioning and remote perconditioning recapitulate cardioprotective effects of local ischemic preconditioning. Am J Physiol Heart Circ Physiol 298:H1819–H1831. doi:10.1152/ajpheart.01102.2009

    Article  PubMed  CAS  Google Scholar 

  60. Zatta AJ, Kin H, Yoshishige D, Jiang R, Wang N, Reeves JG, Mykytenko J, Guyton RA, Zhao ZQ, Caffrey JL, Vinten-Johansen J (2008) Evidence that cardioprotection by postconditioning involves preservation of myocardial opioid content and selective opioid receptor activation. Am J Physiol Heart Circ Physiol 294:H1444–H1451. doi:10.1152/ajpheart.01279.2006

    Article  PubMed  CAS  Google Scholar 

  61. 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 

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Acknowledgments

The authors would like to thank Pierre Legras and Jerome Roux from Service Commun Animalerie Hospitalo-Universitaire for taking care of the animals, Robert Filmon and Romain Mallet from Service Commun d’Imageries et d’Analyses Microscopiques for their technical assistance. Nehmat Ghaboura and Sophie Tamareille were supported by a fellowship from Conseil Général du Maine et Loire. Victor Mateus was supported by a grant from Région Pays de Loire.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. LUNAM Université, Angers, France

    Sophie Tamareille, Victor Mateus, Nehmat Ghaboura, Julien Jeanneteau, Anne Croué, Daniel Henrion, Alain Furber & Fabrice Prunier

  2. Laboratoire Protection et Remodelage du Myocarde, CHU d’Angers, Service de Cardiologie, Université d’Angers, Angers, France

    Sophie Tamareille, Victor Mateus, Nehmat Ghaboura, Julien Jeanneteau, Alain Furber & Fabrice Prunier

  3. Département de Pathologie Cellulaire et Tissulaire, CHU d’Angers, Université d’Angers, Angers, France

    Anne Croué

  4. INSERM U771, CNRS UMR 6214, Université d’Angers, Angers, France

    Daniel Henrion

  5. Protection et Remodelage du Myocarde, UPRES EA 3860, Faculté de Médecine, Rue Haute de Reculée, 49045, Angers Cedex 1, France

    Fabrice Prunier

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  1. Sophie Tamareille
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Tamareille, S., Mateus, V., Ghaboura, N. et al. RISK and SAFE signaling pathway interactions in remote limb ischemic perconditioning in combination with local ischemic postconditioning. Basic Res Cardiol 106, 1329–1339 (2011). https://doi.org/10.1007/s00395-011-0210-z

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