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Authordc.contributor.authorRossello, Xavier 
Authordc.contributor.authorRiquelme, Jaime A. 
Authordc.contributor.authorHe, Zhenhe 
Authordc.contributor.authorTaferner, Stasa 
Authordc.contributor.authorVanhaesebroeck, Bart 
Authordc.contributor.authorDavidson, Sean M. 
Authordc.contributor.authorYellon, Derek M. 
Cita de ítemdc.identifier.citationBasic Res Cardiol (2017) 112: 66es_ES
Abstractdc.description.abstractIschemic preconditioning (IPC) limits myocardial infarct size through the activation of the PI3K-Akt signal cascade; however, little is known about the roles of individual PI3K isoforms in cardioprotection. We aimed, therefore, to elucidate the role of the PI3K alpha isoform in cardioprotection Pharmacological PI3K alpha inhibition was assessed in isolated-perfused mouse hearts subjected to ischemia/reperfusion injury (IRI), either during the IPC procedure or at reperfusion. PI3K alpha inhibition abrogated the IPC-induced protective effect at reperfusion, but not when given only during the IPC protocol. These results were confirmed in an in vivo model. Moreover, pharmacological PI3K alpha activation by insulin at reperfusion was sufficient to confer cardioprotection against IRI. In addition, PI3K alpha was shown to be expressed and activated in mouse cardiomyocytes, mouse cardiac endothelial cells, as well as in mouse and human heart tissue. Furthermore, PI3K alpha was shown to mediate its effect though the inhibition of mitochondrial permeability transition pore opening. In conclusion, PI3K alpha activity is required during the early reperfusion phase to reduce myocardial infarct size. This suggests that strategies specifically enhancing the alpha isoform of PI3K at reperfusion promote tissue salvage and as such, and could provide a direct target for clinical treatment of IRI.es_ES
Patrocinadordc.description.sponsorshipFundacion Rafael del Pino FONDECYT 3160298 British Heart Foundation Cancer Research UK C23338/A15965 UK NIHR University College London Hospitals Biomedical Research Centrees_ES
Type of licensedc.rightsAttribution-NonCommercial-NoDerivs 3.0 Chile*
Link to Licensedc.rights.uri*
Sourcedc.sourceBasic Research in Cardiologyes_ES
Keywordsdc.subjectPhosphoinositide 3 - kinasees_ES
Keywordsdc.subjectIschemic preconditioninges_ES
Keywordsdc.subjectIschemia reperfusion injuryes_ES
Títulodc.titleThe role of PI3K alpha isoform in cardioprotectiones_ES
Document typedc.typeArtículo de revista
Indexationuchile.indexArtículo de publicación ISIes_ES

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Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs 3.0 Chile