| Abstract
| - . Akt/protein kinase B is a key mediator of protection against myocardial ischaemia-reperfusion (I-R) injury. Previous studies have shown that Akt is activated in response to cardioprotective ischaemic preconditioning (IPC) stimulus. However, there are three different Akt isoforms, of which Akt1 and Akt2 are the most abundant in the heart, and it is unclear which isoform is crucial for IPC-induced cardioprotection. The aim of this study was to identify the Akt isoform which is essential for mediating IPC-induced cardioprotection. Mice deficient in Akt1 or Akt2 were subjected to in vivo regional myocardial ischaemia for 30 min followed by reperfusion for 2 h with or without a prior IPC stimulus, comprising 5 min of ischaemia followed by 5 min of reperfusion. Infarct size and area at risk were determined by differential staining with tetrazolium chloride and Evans Blue dye. Mice lacking either single or both alleles for Akt1 were not amenable to IPC (see table 1). In contrast, only mice lacking both alleles for Akt2 were resistant to IPC, whereas mice heterozygous for Akt2 were still amenable to IPC (see table 1). Table 1 Infarct sizes expressed as a percentage of the area at risk+/++/−−/−Akt1 I-R45.5%±2.6%45.3%±5.1%47.2%±7.2% I-R+IPC28.9%±1.4%*40.5%±8.0%37.9%±4.0%Akt2 I-R41.8%±4.0%46.2%±4.7%46.4%±5.6% I-R+IPC30.2%±2.3%120.7%±2.0%135.9%±5.0% * p<0.05 versus respective I-R group. In conclusion, it appears that Akt1 but not Akt2 is essential for cardioprotection conferred by ischaemic preconditioning.
|
