| First Author | Ma L | Year | 2014 |
| Journal | Lab Invest | Volume | 94 |
| Issue | 10 | Pages | 1083-91 |
| PubMed ID | 25046438 | Mgi Jnum | J:214225 |
| Mgi Id | MGI:5588597 | Doi | 10.1038/labinvest.2014.95 |
| Citation | Ma L, et al. (2014) Differential effects of Akt1 signaling on short- versus long-term consequences of myocardial infarction and reperfusion injury. Lab Invest 94(10):1083-91 |
| abstractText | A specific role for Akt1 in events following myocardial infarction (MI) and ischemia/reperfusion (I/R) injury is not known. We aimed to determine whether Akt1 deletion in in vivo mouse models of MI and after ischemia I/R injury would alter myocyte survival, cardiac function, and fibrosis. Akt1(+/+) and Akt1(-/-) mice were subjected to MI and I/R, followed by assessment of downstream signaling events and functional consequences. Although no difference in infarct size following short-term MI was observed between Akt1(+/+) and Akt1(-/-) mice, I/R caused substantially more cardiomyocyte apoptosis and tissue damage in Akt1(-/-) mice compared with Akt1(+/+). Importantly, these effects were reversed upon pretreatment with GSK-3 inhibitor SB415286. Counterintuitively, Akt1(-/-) hearts exhibited improved cardiac function following long-term MI compared with Akt1(+/+) and were associated with reduced fibrosis in the left ventricle (LV). Our results demonstrate that Akt1-mediated inhibition of GSK-3 activity is critical for cardioprotection following I/R. However, in the long term, Akt1 contributes to fibrosis in post-MI hearts and might exacerbate cardiac dysfunction showing dichotomous role for Akt1 in cardiac remodeling after MI. Our data suggest that better understanding of the Akt1/GSK-3 pathway may provide insights for better therapeutic strategies in post-MI tissues. |
