| First Author | Ceci M | Year | 2007 |
| Journal | Cell Death Differ | Volume | 14 |
| Issue | 5 | Pages | 1060-2 |
| PubMed ID | 17237758 | Mgi Jnum | J:139289 |
| Mgi Id | MGI:3807651 | Doi | 10.1038/sj.cdd.4402095 |
| Citation | Ceci M, et al. (2007) Cardiac-specific overexpression of E40K active Akt prevents pressure overload-induced heart failure in mice by increasing angiogenesis and reducing apoptosis. Cell Death Differ 14(5):1060-2 |
| abstractText | Cardiomyocytes (CMC) adapt to physical training by increasing cell size and maintaining cell function, whereas during pressure overload CMC size and function do not increase accordingly. We have previously shown that transgenic mice overexpressing the E40K mutant of Akt (E40K-Akt) present with increased CMC size and improved cardiac function in vivo, and increased inotropism and lusitropism at the cellular level. In this report, we determined the effects of E40K-Akt overexpression on cardiac function after pressure overload induced by transverse aortic constriction (TAC). After TAC, mice overexpressing E40K-Akt (Tg) had a better cardiac function compared to wild type (WT) littermates. In fact, percent fractional shortening (FS%) and dP/dtmax were significantly higher in Tg vs WT mice at 1 and 8 weeks after TAC (at 8 weeks after TAC: FS%: 41.5 vs 26.6, P<0.05; dP/dTmax: 6851+1972 vs 2442+536 mmHg, P<0.05). Differences in âstressâ gene expression, evaluated by quantitative real time PCR, were also evident between Tg and WT animals. Histological analyses showed significantly less fibrosis in Tg vs WT mice; moreover, after TAC, the levels of VEGF protein remained constant in Tg while in WT mice, it was increased at 1 week and decreased at 8 weeks. More strikingly, apoptosis was considerably less in the myocardium of Tg mice when compared to WT animals. Thus, E40K-Akt overexpression maintains cardiac function after TAC. This effect is associated with decreased myocardial apoptosis. These data strongly suggest a protective role of Akt in the myocardium during conditions of stress such as pressure overload. |
