Abstract 18209: Disruption of the Dystrophin-Glycoprotein Complex (DGC) in Human Dilated Cardiomyopathy Improves With Left Ventricular Assist Device (LVAD) Support
Introduction: The DGC, a multimeric protein complex, provides mechanical support to the cardiac membrane during contraction. Mutations in dystrophin leading to loss of the DGC in Duchenne Muscular Dystrophy (DMD) leads to a significant cardiomyopathy, however the role of the DGC has not been evaluated in non-ischemic cardiomyopathy (NICM).
Hypothesis: We hypothesized that similar to DMD cardiomyopathy, in NICM there is also a disruption of the DGC and subsequent loss of structural integrity of cardiomyocytes. The disruption in the DGC may be a result of mechanical loading and could be reversed with unloading the LV.
Materials and Methods: We performed wheat-germ agglutinin pulldown with quantitative western blot analysis in triplicate for DGC components including dystrophin, utrophin, β-dystroglycan, dystrobrevin, syntrophin in age and gender matched human LV samples including: non failing normal, non-failing left ventricular hypertrophy (LVH), NICM, and paired NICM with LVAD supported human LV samples (n =10 for each).
Results: There were no significant differences in DGC components between normal and LVH samples. Dystrophin, utrophin, β-dystroglycan, syntrophin, dystrobrevin, were all significantly reduced in the NICM (average LVEDD 8.3 ± 0.9cm) and pre LVAD samples in comparison to the normal hearts. GAPDH was used as a loading control and there was no significant difference between samples. Following LVAD support with improvement in LV size (average LVEDD 7.94 to 6.76cm, p < 0.001 for average of 608 days) we observed a significant increase in DGC components.
Conclusion: There is a significant reduction in the majority of DGC components in dilated NICM hearts, and these changes are reversed with LVAD therapy. Loss of the DGC may be due to loss of myocardial structural integrity that is reversed with LV unloading with an LVAD. Further studies will need to be performed to determine the mechanism and clinical significance of the DGC reduction in human heart failure.
Author Disclosures: F. Kamdar: None. A. Klaassen Kamdar: None. C.S. Moravec: None. W. Tang: None.
- © 2016 by American Heart Association, Inc.