title: RISK and SAFE signaling pathway involvement in apolipoprotein A-I-induced cardioprotection.
abstract: Recent findings indicate that apolipoprotein A-I (ApoA-I) may be a protective humoral mediator involved in remote ischemic preconditioning (RIPC). This study sought to determine if ApoA-I mediates its protective effects via the RISK and SAFE signaling pathways implicated in RIPC. Wistar rats were allocated to one of the following groups.
  
  
  METHODS
  rats were subjected to myocardial ischemia/reperfusion (I/R) without any further intervention; RIPC: four cycles of limb I/R were applied prior to myocardial ischemia; ApoA-I: 10 mg/Kg of ApoA-I were intravenously injected prior to myocardial ischemia; ApoA-I + inhibitor: pharmacological inhibitors of RISK/SAFE pro-survival kinase (Akt, ERK1/2 and STAT-3) were administered prior to ApoA-I injection. Infarct size was significantly reduced in the RIPC group compared to CONTROL. Similarly, ApoA-I injection efficiently protected the heart, recapitulating RIPC-induced cardioprotection. The ApoA-I protective effect was associated with Akt and GSK-3β phosphorylation and substantially inhibited by pretreatment with Akt and ERK1/2 inhibitors. Pretreatment with ApoA-I in a rat model of I/R recapitulates RIPC-induced cardioprotection and shares some similar molecular mechanisms with those of RIPC-involved protection of the heart.
authors.affiliation: L'UNAM Université, Angers, France; Université d'Angers, Laboratoire Cardioprotection, Remodelage et Thrombose, Angers, France.
authors.forename: Hussein
authors.initials: H
authors.lastname: Kalakech
authors.affiliation: L'UNAM Université, Angers, France; Université d'Angers, Laboratoire Cardioprotection, Remodelage et Thrombose, Angers, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Hibert
authors.affiliation: L'UNAM Université, Angers, France; Université d'Angers, INSERM U771, CNRS UMR 6214, CHU Angers, Département de Biochimie et Génétique, Angers, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Prunier-Mirebeau
authors.affiliation: L'UNAM Université, Angers, France; Université d'Angers, Laboratoire Cardioprotection, Remodelage et Thrombose, Angers, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Tamareille
authors.affiliation: L'UNAM Université, Angers, France; CHU Angers, Laboratoire de Neurobiologie-Neuropathologie, UPRES EA3143, Institut de Biologie en Santé - PBH, Angers, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Letournel
authors.affiliation: L'UNAM Université, Angers, France; Université d'Angers, Laboratoire Cardioprotection, Remodelage et Thrombose, Angers, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Macchi
authors.affiliation: INSERM, U744, Institut Pasteur de Lille, Université Lille Nord de France, Lille, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Pinet
authors.affiliation: L'UNAM Université, Angers, France; Université d'Angers, Laboratoire Cardioprotection, Remodelage et Thrombose, Angers, France; CHU Angers, Service de Cardiologie, Angers, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Furber
authors.affiliation: L'UNAM Université, Angers, France; Université d'Angers, Laboratoire Cardioprotection, Remodelage et Thrombose, Angers, France; CHU Angers, Service de Cardiologie, Angers, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Prunier
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D019157:Ischemic Preconditioning, Myocardial; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017208:Rats, Wistar; D015398:Signal Transduction
chemical_list: D016632:Apolipoprotein A-I; D002316:Cardiotonic Agents; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3