The Akt1 isoform is an essential mediator of ischaemic preconditioning.
Bottom Line: Phosphatidyl-inositol-3-kinase (PI3K)-Akt pathway is essential for conferring cardioprotection in response to ischaemic preconditioning (IPC) stimulus.However, the role of the individual Akt isoforms expressed in the heart in mediating the protective response to IPC is unknown.Akt1 but not Akt2 is essential for mediating a protective response to an IPC stimulus.
Affiliation: The Hatter Cardiovascular Institute, The Institute of Cardiovascular Science, University College London, London, UK.Show MeSH
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Mentions: Ischaemia-reperfusion injury did not result in larger myocardial infarct areas in mice lacking either one or both alleles for the Akt1 gene compared to their littermate control mice (Fig. 3A). We then proceeded to examine whether Akt1 plays a role in mediating the ischaemic preconditioning stimulus. Ischaemic preconditioning resulted in significant protection in Akt1+/+ mice against I-R injury (28.9 ± 1.4% with IPC versus 45.5 ± 2.6% in control, n = 6, P = 0.0001, Fig. 3A, first panel). However, neither Akt1+/− nor Akt1−/− mice were amenable to protection induced by IPC (40.5 ± 7.8% with IPC versus 45.3 ± 5.1% in control, 38.5 ± 1.9 with IPC versus 42.7 ± 6.5% in control, respectively, n = 6, Fig. 3A, middle panels). In addition, increasing the number of IPC cycles from one to three did not result in significant protection in Akt1+/− mice (32.4 ± 3.2% with IPC versus 41.4 ± 6.3% in control, n = 10, NS, Fig. 3A, last panel).
Affiliation: The Hatter Cardiovascular Institute, The Institute of Cardiovascular Science, University College London, London, UK.