Reference : Short-term akt activation in cardiac muscle cells improves contractile function in fa...
Scientific journals : Article
Human health sciences : Endocrinology, metabolism & nutrition
Human health sciences : Cardiovascular & respiratory systems
Short-term akt activation in cardiac muscle cells improves contractile function in failing hearts
Shiojima, I. [> >]
Schiekofer, S. [> >]
Schneider, Jochen mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Belisle, K. [> >]
Sato, K. [> >]
Andrassy, M. [> >]
Galasso, G. [> >]
Walsh, K. [> >]
American Journal of Pathology
American Society for Investigative Pathology
Yes (verified by ORBilu)
[en] Akt is a serine/threonine protein kinase that is activated by a variety of growth factors or cytokines in a phosphatidylinositol 3-kinase-dependent manner. By using a conditional transgenic system in which Akt signaling can be turned on or off in the adult heart, we previously showed that short-term Akt activation induces a physiological form of cardiac hypertrophy with enhanced coronary angiogenesis and maintained contractility. Here we tested the hypothesis that induction of physiological hypertrophy by short-term Akt activation might improve contractile function in failing hearts. When Akt signaling transiently was activated in murine hearts with impaired contractility, induced by pressure overload or doxorubicin treatment, contractile dysfunction was attenuated in both cases. Importantly, improvement of contractility was observed before the development of cardiac hypertrophy, indicating that Akt activation improves contractile function independently of its growth-promoting effects. To gain mechanistic insights into Akt-mediated positive inotropic effects, transcriptional profiles in the heart were determined in a pressure overload-induced heart failure model. Biological network analysis of differentially expressed transcripts revealed significant alterations in the expression of genes associated with cell death, and these alterations were reversed by short-term Akt activation. Thus, short-term Akt activation improves contractile function in failing hearts. This beneficial effect of Akt on contractility is hypertrophy-independent and may be mediated in part by inhibition of cell death associated with heart failure.
Luxembourg Centre for Systems Biomedicine (LCSB): Medical Translational Research (J. Schneider Group)
in press

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