RISK and SAFE Signaling Pathway Involvement in Apolipoprotein A-I-Induced CardioprotectionReportar como inadecuado




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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. Control: 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.



Autor: Hussein Kalakech, Pierre Hibert, Delphine Prunier-Mirebeau, Sophie Tamareille, Franck Letournel, Laurent Macchi, Florence Pinet,

Fuente: http://plos.srce.hr/



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