Apolipoprotein A-I Is a Potential Mediator of Remote Ischemic Preconditioning.docVIP

Apolipoprotein A-I Is a Potential Mediator of Remote Ischemic Preconditioning.doc

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Apolipoprotein A-I Is a Potential Mediator of Remote Ischemic Preconditioning

ApolipoproteinA-IIsaPotentialMediatorofRemote IschemicPreconditioning PierreHibert1,2,DelphinePrunier-Mirebeau1,3,OliviaBeseme4,5,6,MaggyChwastyniak4,5,6 SophieTamareille1,2,DelphineLamon2,AlainFurber1,2,7,FlorencePinet4,5,6,8,FabricePrunier1,2,7 , * 1L’UNAMUniversite′,Angers,France,2LaboratoireCardioprotection,RemodelageetThrombose,Universite′ d’Angers,Angers,France,3INSERMU771,CNRSUMR6214, De′partement de Biochimie et Ge′ne′tique, Universite′ d’Angers, CHU Angers, Angers, France, 4INSERM, U744, Lille, France, 5Institut Pasteur de Lille, Lille, France, 6Universite′ LilleNorddeFrance,IFR142,Lille,France,7ServicedeCardiologie,CHUAngers,Angers,France,8CentreHospitalierRe′gionaletUniversitaire,Lille,France Abstract Background: Remote ischemic preconditioning (RIPC) has emerged as an attractive strategy in clinical settings. Despite convincingevidenceofthecriticalroleplayedbycirculatinghumoralmediators,theiractualidentitiesremainunknown.In thisstudy,weaimedtoidentifyRIPC-inducedhumoralmediatorsusingaproteomicapproach. Methods:andResultsRatswereexposedto10-minlimbischemiafollowedby5-(RIPC59)or10-min(RIPC109 )reperfusion priortobloodsampling.Thecontrolgrouponlyunderwentbloodsampling.Plasmasampleswereanalyzedusingsurface- enhancedlaserdesorptionandionization-timeofflight-massspectrometry(SELDI-TOF-MS).Threeproteinpeakswere selected for their significant increase in RIPC 109. They were identified and confirmed as apolipoprotein A-I (ApoA-I). Additional rats were exposed to myocardial ischemia-reperfusion (I/R) and assigned to one of the following groups RIPC+myocardial infarction (MI) (10-min limb ischemia followed by 10-min reperfusion initiated 20 minutes prior to myocardialI/R),ApoA-I+MI(10mg/kgApoA-Iinjection10minutesbeforemyocardialI/R),andMI(nofurtherintervention). In comparison with untreated MI rats, RIPC reduced infarct size (52.263.7% in RIPC+MI vs. 64.962.6% in MI; p,0.05). Similarly,ApoA-Iinjectiondecreasedinfarctsize(50.963.8%;p,0.05vs .MI). Conclusions:

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