Markers of autophagy are downregulated in failing XXXX heart after mechanical unloading.

@entity1 @entity1522 @entity522 @entity588 @entity19003 @entity33770 @entity10614 @entity1000 @entity8783
BACKGROUND: Autophagy is a molecular process that breaks down damaged cellular organelles and yields @entity1522 for de novo protein synthesis or energy provision. Mechanical unloading with a left ventricular assist device (LVAD) decreases the energy demand of the failing @entity1 heart. We tested the hypothesis that LVAD support reverses activation of autophagy. METHODS AND RESULTS: Paired biopsy samples of left ventricular myocardium were obtained from 9 @entity1 with @entity1000 (mean duration of LVAD support, 214 days) at the time of implantation and explantation of the LVAD. Transcript and protein levels of markers and mediators of autophagy and apoptosis were measured by quantitative reverse-transcription polymerase chain reaction and Western blotting. TUNEL assays, C9 immunohistochemistry, and 20S proteasome activity assays were also performed. Mechanical unloading significantly decreased mRNA transcript levels of @entity8783 , @entity10614 ( @entity10614 ), and microtubule-associated protein-1 light chain-3 (MAP1-LC3 or LC3; P<0.02). Protein levels of @entity8783 , @entity10614 - @entity33770 conjugate, and LC3-II were also significantly reduced after LVAD support (P<0.05). A significant increase in 20S proteasome activity was observed with unloading, in parallel to the decrease in autophagic markers. Although @entity19003 and the ratio of activated @entity522 to @entity522 increased after LVAD support, @entity588 and TUNEL-positive nuclei were not significantly different between samples. CONCLUSIONS: Mechanical unloading of the failing @entity1 heart decreases markers of autophagy. These findings suggest that autophagy may be an adaptive mechanism in the failing heart, and this phenomenon is attenuated by LVAD support.
