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Dynamic regulation of MEK/Erks and Akt/GSK-3β in human end-stage heart failure after left ventricular mechanical support: myocardial mechanotransduction-sensitivity as a possible molecular mechanism
- Source :
- Cardiovascular Research; Aug2003, Vol. 59 Issue 2, p390, 10p
- Publication Year :
- 2003
-
Abstract
- <B>Objective:</B> Left ventricular assist devices (LVAD) are used to ‘bridge’ patients with end-stage heart failure to transplantation. After long-term LVAD support, ventricular function may partially recover, a process called ‘reverse remodeling’. As several kinase-mediated signal transduction pathways have been implicated in the development of cardiac hypertrophy and failure, we examined the activities of the Erks, MEKs, Akt, GSK-3β, p70S6K, JNKs and p38 under LVAD support as well as during single myocyte strain and whole heart stretch. <B>Methods:</B> Western blotting and immunohistochemistry were performed using phospho-specific antibodies in matched samples from ten patients with end-stage heart failure before and after LVAD. Cyclic strain was performed in rat neonatal cardiac myocytes, and tensile stretch applied to Langendorff-perfused mouse hearts via a left ventricular balloon. <B>Results:</B> The activity of Erks and Akt in failing hearts dramatically decreased after LVAD support, while that of GSK-3β increased. There was an endo/epicardial gradient for Erk activity which persisted after LVAD despite the reduction of total Erk activity. TUNEL-positivity and myocyte size decreased after LVAD, but independently of changes in kinase activity. In cardiomyocytes and Langendorff-perfused mouse hearts both strain/stretch and its relief regulated the activities of Erks, Akt, and GSK-3β. <B>Conclusion:</B> Erks and Akt/GSK-3β are highly responsive to myocyte stretch in vitro and in vivo, and may be sensitive molecular parameters of ‘reverse remodeling’ under LVAD support. [Copyright &y& Elsevier]
- Subjects :
- CARDIAC hypertrophy
MUSCLE cells
GENETIC transduction
Subjects
Details
- Language :
- English
- ISSN :
- 00086363
- Volume :
- 59
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Cardiovascular Research
- Publication Type :
- Academic Journal
- Accession number :
- 10427650
- Full Text :
- https://doi.org/10.1016/S0008-6363(03)00393-6