Top

Published in:

Open Access 01-01-2018 | Invited Review

The RISK pathway and beyond

Authors: Xavier Rossello, Derek M. Yellon

Published in: Basic Research in Cardiology | Issue 1/2018

Abstract

Research on cardioprotection has attracted considerable attention during the past 30 years following the discovery of ischemic preconditioning with great advances being made in the field, particularly in the description of the molecular signalling behind this cardioprotective intervention. In a time when basic research is struggling to translate its findings into therapies in the clinical setting, this viewpoint has the intention of presenting to clinical and basic scientists how the reperfusion injury salvage kinase pathway has been described and dissected, as well as highlighting its relevance in cardioprotection.

Alburquerque-Béjar JJ, Barba I, Inserte J, Miró-Casas E, Ruiz-Meana M, Poncelas M, Vilardosa Ú, Valls-Lacalle L, Rodríguez-Sinovas A, Garcia-Dorado D (2015) Combination therapy with remote ischaemic conditioning and insulin or exenatide enhances infarct size limitation in pigs. Cardiovasc Res 107:246–254. https://doi.org/10.1093/cvr/cvv171 CrossRefPubMed

Baxter GF, Mocanu MM, Brar BK, Latchman DS, Yellon DM (2001) Cardioprotective effects of transforming growth factor-beta1 during early reoxygenation or reperfusion are mediated by p42/p44 MAPK. J Cardiovasc Pharmacol 38:930–939CrossRefPubMed

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. https://doi.org/10.1007/s00395-013-0331-7 CrossRefPubMed

Cohen MV, Downey JM (2007) Cardioprotection: spotlight on PKG. Br J Pharmacol 152:833–834. https://doi.org/10.1038/sj.bjp.0707453 CrossRefPubMedPubMedCentral

Davidson SM, Hausenloy D, Duchen MR, Yellon DM (2006) Signalling via the reperfusion injury signalling kinase (RISK) pathway links closure of the mitochondrial permeability transition pore to cardioprotection. Int J Biochem Cell Biol 38:414–419. https://doi.org/10.1016/j.biocel.2005.09.017 CrossRefPubMed

Davidson SM, Yellon DM (2012) STAT5 fits the RISK profile for cardioprotection. JAK-STAT 1:73–76. https://doi.org/10.4161/jkst.20072 CrossRefPubMedPubMedCentral

Fuster V (2014) Top 10 cardiovascular therapies and interventions for the next decade. Nat Rev Cardiol 11:671–683. https://doi.org/10.1038/nrcardio.2014.137 CrossRefPubMed

Gent S, Skyschally A, Kleinbongard P, Heusch G (2017) Ischemic preconditioning in pigs: a causal role for signal transducer and activator of transcription 3. Am J Physiol Heart Circ Physiol 312:H478–H484. https://doi.org/10.1152/ajpheart.00749.2016 CrossRefPubMed

Gersh BJ, Stone GW, White HD, Holmes DR (2005) Pharmacological facilitation of primary percutaneous coronary intervention for acute myocardial infarction: is the slope of the curve the shape of the future? JAMA 293:979–986. https://doi.org/10.1001/jama.293.8.979 CrossRefPubMed

10.

Haq S, Choukroun G, Lim H, Tymitz KM, Del-Monte F, Gwathmey J, Grazette L, Michael A, Hajjar R, Force T, Molkentin JD (2001) Differential activation of signal transduction pathways in human hearts with hypertrophy versus advanced heart failure. Circulation 103:670–677CrossRefPubMed

11.

Hausenloy DJ, Barrabes JA, Botker HE, Davidson SM, Di Lisa F, Downey J, Engstrom T, Ferdinandy P, Carbrera-Fuentes HA, Heusch G, Ibanez B, Iliodromitis EK, Inserte J, Jennings R, Kalia N, Kharbanda R, Lecour S, Marber M, Miura T, Ovize M, Perez-Pinzon MA, Piper HM, Przyklenk K, Schmidt MR, Redington A, Ruiz-Meana M, Vilahur G, Vinten-Johansen J, Yellon DM, Garcia-Dorado D (2016) Ischaemic conditioning and targeting reperfusion injury: a 30 year voyage of discovery. Basic Res Cardiol 111:70. https://doi.org/10.1007/s00395-016-0588-8 CrossRefPubMedPubMedCentral

12.

Hausenloy DJ, Duchen MR, Yellon DM (2003) Inhibiting mitochondrial permeability transition pore opening at reperfusion protects against ischaemia–reperfusion injury. Cardiovasc Res 60:617–625. https://doi.org/10.1016/j.cardiores.2003.09.025 CrossRefPubMed

13.

Hausenloy DJ, Iliodromitis EK, Andreadou I, Papalois A, Gritsopoulos G, Anastasiou-Nana M, Kremastinos DT, Yellon DM (2012) Investigating the signal transduction pathways underlying remote ischemic conditioning in the porcine heart. Cardiovasc Drugs Ther 26:87–93. https://doi.org/10.1007/s10557-011-6364-y CrossRefPubMed

14.

Hausenloy DJ, Tsang A, Mocanu MM, Yellon DM (2005) Ischemic preconditioning protects by activating prosurvival kinases at reperfusion. Am J Physiol Heart Circ Physiol 288:H971–H976. https://doi.org/10.1152/ajpheart.00374.2004 CrossRefPubMed

15.

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. https://doi.org/10.1016/j.tcm.2005.03.001 CrossRefPubMed

16.

Heusch G (2015) Molecular basis of cardioprotection: signal transduction in ischemic pre-, post-, and remote conditioning. Circ Res 116:674–699. https://doi.org/10.1161/CIRCRESAHA.116.305348 CrossRefPubMed

17.

Heusch G, Gersh BJ (2017) The pathophysiology of acute myocardial infarction and strategies of protection beyond reperfusion: a continual challenge. Eur Heart J 38:774–784. https://doi.org/10.1093/eurheartj/ehw224 PubMed

18.

Heusch G, Musiolik J, Kottenberg E, Peters J, Jakob H, Thielmann M (2012) STAT5 activation and cardioprotection by remote ischemic preconditioning in humans novelty and significance. Circ Res 110:111–115. https://doi.org/10.1161/CIRCRESAHA.111.259556 CrossRefPubMed

19.

Inagaki K (2003) Additive protection of the ischemic heart ex vivo by combined treatment with -protein kinase C inhibitor and -protein kinase C activator. Circulation 108:869–875. https://doi.org/10.1161/01.CIR.0000081943.93653.73 CrossRefPubMed

20.

Jonassen AK, Sack MN, Mjøs OD, Yellon DM (2001) Myocardial protection by insulin at reperfusion requires early administration and is mediated via Akt and p70s6 kinase cell-survival signaling. Circ Res 89:1191–1198. https://doi.org/10.1161/hh2401.101385 CrossRefPubMed

21.

Konstantinidis K, Whelan RS, Kitsis RN (2012) Mechanisms of cell death in heart disease. Arterioscler Thromb Vasc Biol 32:1552–1562. https://doi.org/10.1161/ATVBAHA.111.224915 CrossRefPubMed

22.

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

23.

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

24.

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. https://doi.org/10.1016/j.yjmcc.2009.03.019 CrossRefPubMed

25.

Lecour S, Suleman N, Deuchar GA, Somers S, Lacerda L, Huisamen B, Opie LH (2005) Pharmacological preconditioning with tumor necrosis factor-alpha activates signal transducer and activator of transcription-3 at reperfusion without involving classic prosurvival kinases (Akt and extracellular signal-regulated kinase). Circulation 112:3911–3918. https://doi.org/10.1161/CIRCULATIONAHA.105.581058 CrossRefPubMed

26.

McCully JD, Wakiyama H, Hsieh Y-J, Jones M, Levitsky S (2004) Differential contribution of necrosis and apoptosis in myocardial ischemia–reperfusion injury. Am J Physiol Heart Circ Physiol 286:H1923–H1935. https://doi.org/10.1152/ajpheart.00935.2003 CrossRefPubMed

27.

Mensah K, Mocanu MM, Yellon DM (2005) Failure to protect the myocardium against ischemia/reperfusion injury after chronic atorvastatin treatment is recaptured by acute atorvastatin treatment: a potential role for phosphatase and tensin homolog deleted on chromosome ten? J Am Coll Cardiol 45:1287–1291. https://doi.org/10.1016/j.jacc.2005.01.021 CrossRefPubMed

28.

Mocanu MM, Baxter GF, Yellon DM (2000) Caspase inhibition and limitation of myocardial infarct size: protection against lethal reperfusion injury. Br J Pharmacol 130:197–200. https://doi.org/10.1038/sj.bjp.0703336 CrossRefPubMedPubMedCentral

29.

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

30.

Nagoshi T, Matsui T, Aoyama T, Leri A, Anversa P, Li L, Ogawa W, Del-Monte F, Gwathmey JK, Grazette L, Hemmings BA, Hemmings B, Kass DA, Champion HC, Rosenzweig A (2005) PI3K rescues the detrimental effects of chronic Akt activation in the heart during ischemia/reperfusion injury. J Clin Invest 115:2128–2138. https://doi.org/10.1172/JCI23073 CrossRefPubMedPubMedCentral

31.

Rossello X, Riquelme JA, Davidson SM, Yellon DM (2017) Role of PI3K in myocardial ischaemic preconditioning: mapping pro-survival cascades at the trigger phase and at reperfusion. J Cell Mol Med. https://doi.org/10.1111/jcmm.13394 PubMed

32.

Rossello X, Riquelme JA, He Z, Taferner S, Vanhaesebroeck B, Davidson SM, Yellon DM (2017) The role of PI3Kα isoform in cardioprotection. Basic Res Cardiol 112:66. https://doi.org/10.1007/s00395-017-0657-7 CrossRefPubMedPubMedCentral

33.

Rossello X, Yellon DM (2016) A critical review on the translational journey of cardioprotective therapies! Int J Cardiol 220:176–184. https://doi.org/10.1016/j.ijcard.2016.06.131 CrossRefPubMed

34.

Schulman D, Latchman DS, Yellon DM (2002) Urocortin protects the heart from reperfusion injury via upregulation of p42/p44 MAPK signaling pathway. Am J Physiol Heart Circ Physiol 283:H1481–H1488. https://doi.org/10.1152/ajpheart.01089.2001 CrossRefPubMed

35.

Sivaraman V, Hausenloy DJ, Wynne AM, Yellon DM (2010) Preconditioning the diabetic human myocardium. J Cell Mol Med 14:1740–1746. https://doi.org/10.1111/j.1582-4934.2009.00796.x CrossRefPubMed

36.

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. https://doi.org/10.1161/CIRCRESAHA.108.186429 CrossRefPubMed

37.

Skyschally A, Gent S, Amanakis G, Schulte C, Kleinbongard P, Heusch G (2015) Across-species transfer of protection by remote ischemic preconditioning with species-specific myocardial signal transduction by reperfusion injury salvage kinase and survival activating factor enhancement pathways novelty and significance. Circ Res 117:279–288. https://doi.org/10.1161/CIRCRESAHA.117.306878 CrossRefPubMed

38.

Smith CCT, Yellon DM (2011) Necroptosis, necrostatins and tissue injury. J Cell Mol Med 15:1797–1806. https://doi.org/10.1111/j.1582-4934.2011.01341.x CrossRefPubMedPubMedCentral

39.

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. https://doi.org/10.1093/cvr/cvn067 CrossRefPubMed

40.

Takahashi M (2011) Role of the inflammasome in myocardial infarction. Trends Cardiovasc Med 21:37–41. https://doi.org/10.1016/j.tcm.2012.02.002 CrossRefPubMed

41.

Wever KE, Hooijmans CR, Riksen NP, Sterenborg TB, Sena ES, Ritskes-Hoitinga M, Warlé MC (2015) Determinants of the efficacy of cardiac ischemic preconditioning: a systematic review and meta-analysis of animal studies. PLoS ONE 10:e0142021. https://doi.org/10.1371/journal.pone.0142021 CrossRefPubMedPubMedCentral

42.

Wever KE, Menting TP, Rovers M, van der Vliet JA, Rongen GA, Masereeuw R, Ritskes-Hoitinga M, Hooijmans CR, Warlé M (2012) Ischemic preconditioning in the animal kidney, a systematic review and meta-analysis. PLoS ONE 7:e32296. https://doi.org/10.1371/journal.pone.0032296 CrossRefPubMedPubMedCentral

43.

Yellon DM, Alkhulaifi AM, Pugsley WB (1993) Preconditioning the human myocardium. Lancet 342:276–277. https://doi.org/10.1016/0140-6736(93)91819-8 CrossRefPubMed

44.

Yellon DM, Baxter GF (1999) Reperfusion injury revisited: is there a role for growth factor signaling in limiting lethal reperfusion injury? Trends Cardiovasc Med 9:245–249CrossRefPubMed

45.

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

Title: The RISK pathway and beyond
Authors: Xavier Rossello
Derek M. Yellon
Publication date: 01-01-2018
Publisher: Springer Berlin Heidelberg
Published in: Basic Research in Cardiology / Issue 1/2018
Print ISSN: 0300-8428
Electronic ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-017-0662-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The RISK pathway and beyond

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2018

Periostin in cardiovascular disease and development: a tale of two distinct roles

STAT3 as a common signal of ischemic conditioning: a lesson on “rigor and reproducibility” in preclinical studies on cardioprotection

Pre- and postconditioning the heart with hydrogen sulfide (H2S) against ischemia/reperfusion injury in vivo: a systematic review and meta-analysis

Role of NLRP3 inflammasome in the pathogenesis of cardiovascular diseases

AMPK-dependent nitric oxide release provides contractile support during hyperosmotic stress

Gene expression analysis to identify mechanisms underlying heart failure susceptibility in mice and humans