Abstract 16233: Markers of Endoplasmic Reticulum Stress Are Downregulated in Failing Human Hearts After Left Ventricular Assist Device Implantation
Background: We have recently demonstrated that load-induced contractile dysfunction and endoplasmic reticulum (ER) stress are mediated by the accumulation of intermediary glucose metabolite glucose 6-phosphate (G6P) in the rodent heart. In the failing human heart, both glucose metabolism and markers of ER stress are upregulated as well. Mechanical unloading of the failing human heart improves contractile function of the failing left ventricular myocardium. We now tested the hypothesis that the functional improvement is mediated by changes in glucose metabolism and reduction of ER stress.
Methods: Paired biopsy samples of left ventricular myocardium were obtained from 11 non-diabetic patients with idiopathic dilated cardiomyopathy placed on left ventricular assist device (LVAD) support for 254±63 days (mean±SEM). Transmural tissue samples from the apex were immediately frozen at the time of LVAD placement and removal. Intermediary glucose metabolite levels were assessed by spectrophotometric enzymatic analyses. Markers of ER stress were assessed by western blotting.
Results: LVAD support normalized left ventricle end diastolic dimensions. Accumulation of intermediary glucose metabolite G6P was significantly decreased after mechanical unloading with LVAD (Figure 1). Intermediary glucose metabolite levels correlated with a downregulation of protein levels of ER stress markers ERP72, GRP94, and GRP78 (Figure 2).
Conclusion: These data suggest that functional improvement of the failing heart by mechanical unloading with LVAD may be mediated by metabolic unloading and relief of ER stress.
- © 2011 by American Heart Association, Inc.