The role of PI3K alpha isoform in cardioprotection
Author
dc.contributor.author
Rossello, Xavier
Author
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Riquelme, Jaime A.
Author
dc.contributor.author
He, Zhenhe
Author
dc.contributor.author
Taferner, Stasa
Author
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Vanhaesebroeck, Bart
Author
dc.contributor.author
Davidson, Sean M.
Author
dc.contributor.author
Yellon, Derek M.
Admission date
dc.date.accessioned
2018-06-11T17:21:51Z
Available date
dc.date.available
2018-06-11T17:21:51Z
Publication date
dc.date.issued
2017
Cita de ítem
dc.identifier.citation
Basic Res Cardiol (2017) 112: 66
es_ES
Identifier
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10.1007/s00395-017-0657-7
Identifier
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https://repositorio.uchile.cl/handle/2250/148760
Abstract
dc.description.abstract
Ischemic 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
Patrocinador
dc.description.sponsorship
Fundacion Rafael del Pino
FONDECYT
3160298
British Heart Foundation
Cancer Research UK
C23338/A15965
UK NIHR University College London Hospitals Biomedical Research Centre