Abstract 959: Myostatin Regulation in Patients with Advanced Heart Failure and After Mechanical Unloading
Background: Myostatin inhibits myoblast differentiation and myocyte proliferation via cell cycle regulation. Upregulation of myostatin is seen after mycocyte stretch and may play a role in hypertrophy in congestive heart failure (CHF) and reverse remodeling after left ventricular assist device (LVAD) support. The objective of this study was to characterize myostatin expression in patients with advanced CHF before and after LVAD support.
Methods: Left ventricular tissue pairs were collected at LVAD implantation (Core) and after LVAD support at cardiac transplantation/LVAD explantation in patients with severe non-ischemic CHF (DCM, n=6). Normal cardiac tissue was obtained from normal hearts not placed for transplantation (Norm, n=4). Myostatin full-length (FL) and cleaved propeptide (PP) levels were quantified by Western blot analysis using an antibody raised against a sequence in the propeptide region and normalized to actin levels as a loading control. Protein levels are expressed as normalized units.
Results: The duration of CHF was 69.9 ± 73.5 months; the duration of LVAD support was 106.7 ± 77.3 days. DCM PP levels at Core (0.47 ± 0.10) were significantly higher than Norm (0.28 ± 0.09, p=0.016) and significantly increased after LVAD support (0.72 ± 0.34, p=0.009). No change in FL at Core (0.98 ± 0.32) was seen vs. Norm (1.13 ± 0.45) or after LVAD support (1.09 ± 0.74)(both p=NS). A correlation between higher PP levels and increasing duration of LVAD support was seen (R2=0.876, p=0.02).
Conclusions: Myostatin PP expression, upregulated in CHF, is increased with LVAD support and may mediate regression of cellular hypertrophy after mechanical unloading. Further study into regulation of myostatin activation and downstream pathway signaling is warranted.