We wish to comment on the report by Baba et al.[1] The authors measured the activity of several kinases that are involved in the regulation of hypertrophy and apoptosis in the failing human heart before and after mechanical unloading with a left ventricular assist device (LVAD)[1]. They found that the activity of Erks and Akt in the failing human heart decreased after LVAD support, while that of glycogen synthase kinase-3h (GSK-3h) increased. These changes were independent of the decrease in TUNNEL positivity and the decrease in myocyte size. In addition, the authors showed an endo/epicardial gradient for Erk activity in the failing human heart. They go on to conclude that Erks and Akt/GSK-3h are sensitive molecular markers of reverse remodeling under LVAD support. In order to address mechanisms of reverse remodeling, the first condition is the ability to obtain reproducible results. This condition is not easily met in the failing human heart.

We have recently investigated the activity of the Akt/GSK-3h pathway in the same setting as well [2]. Consistent with the study by Baba et al. we found a decrease in myocyte size and a decrease of phosphorylated Erk after mechanical unloading. However, we did not find any significant differences in the total amount or the phosphorylated fraction of Akt or GSK-3h. Our findings are consistent with a study by Chen et al.[3] that also did not find any significant changes in total or phosphorylated Akt protein after LVAD support.