Cardioprotection against reperfusion injury: updated mechanisms and strategies

( views:96, downloads:0 )
Author:
XI Jin-Kun()
JIN Yuan-Zhe()
CUI Xun()
XU Zhe-Long(XU Zhe-Long,Corresponding author. Tel: +1-919-8434174; Fax: +1-919-8433805; Email: zxu@aims.unc.edu)
Journal Title:
ACTA PHYSIOLOGICA SINICA
Issue:
Volume 59, Issue 05, 2007
DOI:
Key Word:
reperfusion injury; cardioprotection; G protein-coupled receptor; insulin; ischemic postconditioning; mitochondrial permeability transition pore

Abstract: Early restoration of blood flow to the ischemic myocardium not only saves myocardium but also induces reperfusion injury.While no specific therapy to reduce reperfusion injury has yet been established, recent laboratory studies have shown that G proteincoupled receptor (GPCR) agonists, insulin, and postconditioning can effectively prevent reperfusion injury in various experimental settings and animal species. The potential mechanisms underlying the cardioprotection initiated by these interventions may include activation of the reperfusion injury salvage kinase (RISK) pathway, inactivation of glycogen synthase kinase 3β (GSK-3β), and modulation of mitochondrial permeability transition pore (mPTP) opening. These encouraging laboratory findings may help us develop successful clinical strategies to salvage reperfused myocardium in patients with acute myocardial infarction.

  • [1]Braunwald E,Kloner RA.Myocardial reperfusion:a doubleedged sword? J Clin Invest 1985; 76:1713-1719.
  • [2]Olah ME,Stiles GL.Adenosine receptor subtypes:characterization and therapeutic regulation.Annu Rev Pharmacol Toxicol 1995; 35:581-606.
  • [3]Headrick JP,Hack B,Ashton KJ.Acute adenosinergic cardioprotection in ischemic-reperfused hearts.Am J Physiol 2003; 285:H1797-H1818.
  • [4]Liu GS,Thornton J,Van Winkle DM,Stanley AWH,Olsson RA,Downey JM.Protection against infarction afforded by preconditioning is mediated by A1 adenosine receptors in rabbit heart.Circulation 1991; 84:350-356.
  • [5]Cohen MV,Baines CP,Downey JM.Ischemic preconditioning:from adenosine receptor to KATP channel.Annu Rev Physiol 2000; 62:79-109.
  • [6]Armstrong S,Ganote CE.Adenosine receptor specificity in preconditioning of isolated rabbit cardiomyocytes:evidence of A3 receptor involvement.Cardiovasc Res 1994; 28:1049-1056.
  • [7]Thornton JD,Liu GS,Olsson RA,Downey JM.Intravenous pretreatment with A1-selective adenosine analogues protects the heart against infarction.Circulation 1992; 85:659-665.
  • [8]Auchampach JA,Rizvi A,Qiu Y,Tang XL,Maldonado C,Teschner S,Bolli R.Selective activation of A3 adenosine receptors with N6-(3-iodobenzyl)adenosine-5'-N-methyluronamide protects against myocardial stunning and infarction without hemodynamic changes in conscious rabbits.Circ Res 1997; 80:800-809.
  • [9]Zhao ZQ,McGee S,Nakanishi K,Toombs CF,Johnston WE,Ashar MS,Vinten-Johansen J.Receptor-mediated cardioprotective effects of endogenous adenosine are exerted primarily during reperfusion after coronary occlusion in the rabbit.Circulation 1993; 88:709-719.
  • [10]Norton ED,Jackson EK,Turner MB,Virmani R,Forman MB.The effects of intravenous infusions of selective adenosine A1-receptor and A2-receptor agonists on myocardial reperfusion injury.Am Heart J 1992; 123:332-338.
  • [11]Schlack W,Sch(a)fer M,Uebing A,Sch(a)fer S,Borchard U,Thamer V.Adenosine A2-receptor activation at reperfusion reduces infarct size and improves myocardial wall function in dog heart.J Cardiovasc Pharmacol 1993; 22:89-96.
  • [12]Zhao ZQ,Sato H,Williams MW,Fernandez AZ,VintenJohansen J.Adenosine A2-receptor activation inhibits neutrophil-mediated injury to coronary endothelium.Am J Physiol 1996; 271:H1456-H1464.
  • [13]Jordan JE,Zhao ZQ,Sato H,Taft S,Vinten-Johansen J.Adenosine A2 receptor activation attenuates reperfusion injury by inhibiting neutrophil accumulation,superoxide generation and coronary endothelial adherence.J Pharmacol Exp Ther 1997;280:301-309.
  • [14]Smits GJ,McVey M,Cox BF,Perrone MH,Clark KL.Cardioprotective effects of the novel adenosine A1/A2 receptor agonist AMP 579 in a porcine model of myocardial infarction.J Pharmacol Exp Ther 1998; 286:611-618.
  • [15]Budde JM,Velez DA,Zhao Z,Clark KL,Morris CD,Muraki S,Guyton RA,Vinten-Johansen J.Comparative study of AMP579and adenosine in inhibition of neutrophil-mediated vascular and myocardial injury during 24 h of reperfusion.Cardiovasc Res 2000; 47:294-305.
  • [16]Xu Z,Yang XM,Cohen MV,Neumann T,Heusch G,Downey JM.Limitation of infarct size in rabbit hearts by the novel adenosine receptor agonist AMP 579 administered at reperfusion.J Mol Cell Cardiol 2000; 32:2339-2347.
  • [17]Xu Z,Downey JM,Cohen MV.AMP 579 reduces contracture and limits infarction in rabbit heart by activating adenosine A2 receptors.J Cardiovasc Pharmacol 2001; 38:474-481.
  • [18]Xu Z,Jiao Z,Cohen MV,Downey JM.Protection from AMP 579 can be added to that from either cariporide or ischemic preconditioning in ischemic rabbit heart.J Cardiovasc Pharmacol 2002; 40:510-518.
  • [19]Feoktistov I,Biaggioni I.Adenosine A2B receptors.Pharmacol Rev 1997; 49:381-402.
  • [20]Auchampach JA,Ge ZD,Wan TC,Moore J,Gross GJ.A3 adenosine receptor agonist IB-MECA reduces myocardial ischemia-reperfusion injury in dogs.Am J Physiol 2003; 285:H607-H613.
  • [21]Gardner NM,Yates L,Broadley KJ.Effects of endogenous adenosine and adenosine receptor agonists on hypoxia-induced myocardial stunning in guinea-pig atria and papillary muscles.J Cardiovasc Pharmacol 2004; 43:358-368.
  • [22]Maddock HL,Gardner NM,Khandoudi N,Bril A,Broadley KJ.Protection from myocardial stunning by ischaemia and hypoxia with the adenosine A3 receptor agonist,IB-MECA.Eur J Pharmacol 2003; 477:235-245.
  • [23]Maddock HL,Mocanu MM,Yellon DM.Adenosine A3 receptor activation protects the myocardium from reperfusion/reoxygenation injury.Am J Physiol 2002; 283:H1307-H1313.
  • [24]Park SS,Zhao H,Jang Y,Mueller RA,Xu Z.N6-(3-iodobenzyl)-adenosine-5'-N-methylcarboxamide confers cardioprotection at reperfusion by inhibiting mitochondrial permeability transition pore opening via glycogen synthase kinase 3β.J Pharmacol Exp Ther 2006; 318:124-131.
  • [25]Goto M,Liu Y,Yang XM,Ardell JL,Cohen MV,Downey JM.Role of bradykinin in protection of ischemic preconditioning in rabbit hearts.Circ Res 1995; 77:611-621.
  • [26]Bell RM,Yellon DM.Bradykinin limits infarction when administered as an adjunct to reperfusion in mouse heart:the role of PI3K,Akt and eNOS.J Mol Cell Cardiol 2003; 35:185-193.
  • [27]Park SS,Zhao H,Mueller R,Xu Z.Bradykinin prevents reperfusion injury by targeting mitochondrial permeability transition pore through glycogen synthase kinase 3β.J Mol Cell Cardiol 2006; 40:708-716.
  • [28]Lim SY,Davidson SM,Hausenloy DJ,Yellon DM.Preconditioning and postconditioning:The essential role of the mitochondrialpermeability transition pore.Cardiovasc Res 2007; 75:530-535.
  • [29]Penna C,Mancardi D,Rastaldo R,Losano G,Pagliaro P.Intermittent activation of bradykinin B2 receptors and mitochondrial KATP channels trigger cardiac postconditioning through redox signaling.Cardiovasc Res 2007; 75:168-177.
  • [30]Gross GJ.Role of opioids in acute and delayed preconditioning.J Mol Cell Cardiol 2003; 35:709-718.
  • [31]Schultz JE,Hsu AK,Gross GJ.Ischemic preconditioning in the intact rat heart is mediated by deltal-but not mu-or kappaopioid receptors.Circulation 1998; 97:1282-1289.
  • [32]Schultz JJ,Hsu AK,Nagase H,Gross GJ.TAN-67,a deltaopioid receptor agonist,reduces infarct size via activation of Gi/o proteins and KATP channels.Am J Physiol 1998; 274:H909-H914.
  • [33]Wu S,Li HY,Wong TM.Cardioprotection of preconditioning by metabolic inhibition in the rat ventricular myocyte.Circ Res 1999; 84:1388-1395.
  • [34]Gross ER,Hsu AK,Gross GJ.Opioid-induced cardioprotection occurs via glycogen synthase kinase βinhibition during reperfusion in intact rat hearts.Circ Res 2004; 94:960-966.
  • [35]Gross E,Hsu A,Gross G.GSK3β inhibition and KATP channel opening mediate acute opioid-induced cardioprotection at reperfusion.Basic Res Cardiol 2007; 102:341-349.
  • [36]Zhao ZQ,Corvera JS,Halkos ME,Kerendi F,Wang NP,Guyton RA,Vinten-Johansen J.Inhibition of myocardial injury by ischemic postconditioning during reperfusion:comparison with ischemic preconditioning.Am J Physiol Heart Circ Physiol 2003;285:H579-H588.
  • [37]Kin H,Zhao ZQ,Sun HY,Wang NP,Corvera JS,Halkos ME,Kerendi F,Guyton RA,Vinten-Johansen J.Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion.Cardiovasc Res 2004;62:74-85.
  • [38]Kin H,Zatta AJ,Lofye MT,Amerson BS,Halkos ME,Kerendi F,Zhao ZQ,Guyton RA,Headrick JP,Vinten-Johansen J.Postconditioning reduces infarct size via adenosine receptor activation by endogenous adenosine.Cardiovasc Res 2005; 67:124-133.
  • [39]Galagudza M,Kurapeev D,Minasian S,Valen G,Vaage J.Ischemic postconditioning:brief ischemia during reperfusion converts persistent ventricular fibrillation into regular rhythm.Eur J Cardiothorac Surg 2004; 25:1006-1010.
  • [40]Tsang A,Hausenloy DJ,Mocanu MM,Yellon DM.Postconditioning:A form of"modified reperfusion" protects the myocardium by activating the phosphatidylinositol 3-kinase-Akt pathway.Circ Res 2004; 95:230-232.
  • [41]Yang XM,Proctor JB,Cui L,Krieg T,Downey JM,Cohen MV.Multiple,brief coronary occlusions during early reperfusion protect rabbit hearts by targeting cell signaling pathways.J Am Coll Cardiol 2004; 44:1103-1110.
  • [42]Yang XM,Philipp S,Downey JM,Cohen MV.Postconditioning's protection is not dependent on circulating blood factors or cells but involves adenosine receptors and requires PI3-kinase and guanylyl cyclase activation.Basic Res Cardiol 2005; 100:57-63.
  • [43]Argaud L,Gateau-Roesch O,Raisky O,Loufouat J,Robert D,Ovize M.Postconditioning inhibits mitochondrial permeability transition.Circulation 2005; 111:194-197.
  • [44]Serviddio G,Di Venosa N,Federici A,D'Agostino D,Rollo T,Prigigallo F,Altomare E,Fiore T,Vendemiale G.Brief hypoxia before normoxic reperfusion (postconditioning) protects the heart against ischemia-reperfusion injury by preventing mitochondria peroxyde production and glutathione depletion.FASEB J 2005;19:354-361.
  • [45]Sun HY,Wang NP,Halkos M,Kerendi F,Kin H,Guyton RA,Vinten-Johansen J,Zhao ZQ.Postconditioning attenuates cardiomyocyte apoptosis via inhibition of JNK and p38 mitogenactivated protein kinase signaling pathways.Apoptosis 2006; 11:1583-1593.
  • [46]Sun HY,Wang NP,Kerendi F,Halkos M,Kin H,Guyton RA,Vinten-Johansen J,Zhao ZQ.Hypoxic postconditioning reduces cardiomyocyte loss by inhibiting ROS generation and intracellular Ca2+ overload.Am J Physiol 2005; 288:H1900-H1908.
  • [47]Darling CE,Jiang R,Maynard M,Whittaker P,Vinten-Johansen J,Przyklenk K.Postconditioning via stuttering reperfusion limits myocardial infarct size in rabbit hearts:role of ERK1/2.Am J Physiol Heart Circ Physiol 2005; 289:H1618-H1626.
  • [48]Zhao ZQ,Vinten-Johansen J.Postconditioning:Reduction of reperfusion-induced injury.Cardiovasc Res 2006; 70:200-211.
  • [49]Hausenloy DJ,Yellon DM.Survival kinases in ischemic preconditioning and postconditioning.Cardiovasc Res 2006; 70:240-253.
  • [50]Philipp S,Yang XM,Cui L,Davis AM,Downey JM,Cohen MV.Postconditioning protects rabbit hearts through a protein kinase C-adenosine A2b receptor cascade.Cardiovasc Res 2006;70:308-314.
  • [51]Zatta AJ,Kin H,Lee G,Wang N,Jiang R,Lust R,Reeves JG,Mykytenko J,Guyton RA,Zhao ZQ,Vinten-Johansen J.Infarct-sparing effect of myocardial postconditioning is dependent on protein kinase C signalling.Cardiovasc Res 2006; 70:315-324.
  • [52]Gateau-Roesch O,Argaud L,Ovize M.Mitochondrial permeability transition pore and postconditioning.Cardiovasc Res 2006;70:264-273.
  • [53]Cohen MV,Yang XM,Downey JM.The pH hypothesis of postconditioning:staccato reperfusion reintroduces oxygen and perpetuates myocardial acidosis.Circulation 2007; 115:1895-1903.
  • [54]Jonassen AK,Aasum E,Riemersma RA,Mjos OD,Larsen TS.Glucose-insulin-potassium reduces infarct size when administered during reperfusion.Cardiovasc Drugs Ther 2000; 14:615-623.
  • [55]Jonassen AK,Sack MN,Mjos OD,Yellon DM.Myocardial protection by insulin at reperfusion requires early administration and is mediated via Akt and p70s6 kinase cell-survival signaling.Circ Res 2001; 89:1191-1198.
  • [56]Gao F,Gao E,Yue TL,Ohlstein EH,Lopez BL,Christopher TA,Ma XL.Nitric oxide mediates the antiapoptotic effect of insulin in myocardial ischemia-reperfusion:the roles of PI3-kinase,Akt,and endothelial nitric oxide synthase phosphorylation.Circulation 2002; 105:1497-1502.
  • [57]Jonassen AK,Brar BK,Mjos OD,Sack MN,Latchman DS,Yellon DM.Insulin administered at reoxygenation exerts a cardioprotective effect in myocytes by a possible anti-apoptotic mechanism.J Mol Cell Cardiol 2000; 32:757-764.
  • [58]Hausenloy DJ,Yellon DM.New directions for protecting the heart against ischaemia-reperfusion injury:targeting the Reperfusion Injury Salvage Kinase (RISK)-pathway.Cardiovasc Res 2004; 61:448-460.
  • [59]Gross GJ,Auchampach JA.Reperfusion injury:Does it exist? J Mol Cell Cardiol 2007; 42:12-18.
  • [60]Kis A,Baxter GF,Yellon DM.Limitation of myocardial reperfusion injury by AMP579,an adenosine A1/A2A receptor agonist:role of A2A receptor and Erk1/2.Cardiovasc Drugs Ther 2003; 17:415-425.
  • [61]Kroemer G,Dallaporta B,Resche-Rigon M.The mitochondrial death/life regulator in apoptosis and necrosis.Annu Rev Physiol 1998; 60:619-642.
  • [62]Suleiman MS,Halestrap AP,Griffiths EJ.Mitochondria:a target for myocardial protection.Pharmacol Ther 2001; 89:29-46.
  • [63]Crompton M.The mitochondrial permeability transition pore and its role in cell death.Biochem J 1999; 341:233-249.
  • [64]Halestrap AP,Clarke SJ,Javadov SA.Mitochondrial permeability transition pore opening during myocardial reperfusion-a target for cardioprotection.Cardiovasc Res 2004; 61:372-385.
  • [65]Weiss JN,Korge P,Honda HM,Ping P.Role of the mitochondrial permeability transition in myocardial disease.Circ Res 2003;93:292-301.
  • [66]Piper HM,García-Dorado D,Ovize M.A fresh look at reperfusion injury.Cardiovasc Res 1998; 38:291-300.
  • [67]Park JL,Lucchesi BR.Mechanisms of myocardial reperfusion injury.Ann Thor Surg 1999; 68:1905-1912.
  • [68]Griffiths EJ,Halestrap AP.Mitochondrial non-specific pores remain closed during cardiac ischaemia,but open upon reperfusion.Biochem J 1995; 307:93-98.
  • [69]Griffiths EJ,Halestrap AP.Protection by cyclosporin A of ischemia/reperfusion-induced damage in isolated rat hearts.J Mol Cell Cardiol 1993; 25:1461-1469.
  • [70]Griffiths EJ,Ocampo CJ,Savage JS,Stern MD,Silverman HS.Protective effects of low and high doses of cyclospodn A against reoxygenation injury in isolated rat cardiomyocytes are associated with differential effects on mitochondrial calcium levels.Cell Calcium 2000; 27:87-95.
  • [71]Xu Z,Park SS,Mueller RA,Bagnell RC,Patterson C,Boysen PG.Adenosine produces nitric oxide and prevents mitochondrial oxidant damage in rat cardiomyocytes.Cardiovasc Res 2005; 65:803-812.
  • [72]Feng J,Lucchinetti E,Ahuja P,Pasch T,Perriard JC,Zaugg M.Isoflurane postconditioning prevents opening of the mitochondrial permeability transition pore through inhibition of glycogen synthase kinase 3β.Anesthesiology 2005; 103:987-995.
  • [73]Davidson SM,Hausenloy D,Duchen MR,Yellon DM.Signalling via the reperfusion injury signalling kinase (RISK) pathway links closure of the mitochondrial permeability transition pore to cardioprotection.Int J Biochem Cell Biol 2006; 38:414-419.
  • [74]Juhaszova M,Zorov DB,Kim SH,Pepe S,Fu Q,Fishbein KW,Ziman BD,Wang S,Ytrehus K,Antos CL,Olson EN,Sollott SJ.Glycogen synthase kinase-3β mediates convergence of protection signaling to inhibit the mitochondrial permeability transition pore.J Clin Invest 2004; 113:1535-1549.
  • [75]Frame S,Cohen P.GSK3 takes centre stage more than 20 years after its discovery.Biochem J 2001; 359:1-16.
  • [76]Cohen P,Frame S.The renaissance of GSK3.Nat Rev Mol Cell Biol 2001; 2:769-776.
  • [77]Murphy E.Inhibit GSK-3β or there's heartbreak dead ahead.J Clin Invest 2004; 113:1526-1528.
  • [78]Tong H,Imahashi K,Steenbergen C,Murphy E.Phosphorylation of glycogen synthase kinase-3β during preconditioning through a phosphatidylinositol-3-kinase-dependent pathway is cardioprotective.Circ Res 2002; 90:377-379.
WanfangData CO.,Ltd All Rights Reserved
About WanfangData | Contact US
Healthcare Department, Fuxing Road NO.15, Haidian District Beijing, 100038 P.R.China
Tel:+86-010-58882616 Fax:+86-010-58882615 Email:yiyao@wanfangdata.com.cn