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Core 5. Myocardium: Function and Failure
Session Title: New Insights into Myocardial Structure and Pathology

Abstract 16765: Myostatin Activity After Prolonged Left Ventricular Assist Device Support is Associated With Dysregulated Structural Muscle Protein Expression and Cardiac Fibrosis

Originally publishedCirculation. 2013;128:A16765

    Background: Myostatin (MSTN) is known to increase fibrosis in skeletal muscle and induces atrophy by altering numerous muscle-specific structural proteins. However, its effect on cardiac muscle protein expression is unknown. The objective of this study was to characterize the effect of MSTN expression on the cardiac muscle profile and fibrosis in patients with advanced heart failure (HF) before and after prolonged left ventricular assist device (LVAD) support.

    Methods: LV apex tissue pairs were collected in patients with dilated cardiomyopathy (n=15) at LVAD implantation and after LVAD support at cardiac transplantation/LVAD explantation. Normal cardiac tissue was obtained from normal hearts (n=4). MSTN propeptide (PP) levels, pSMAD2, MMP9, desmin, actin, and myosin heavy chain smooth muscle (MHC SM), were quantified by Western blot analysis. Fibrosis was quantified from 5 independent H&E cross-sections from each sample (n=13).

    Results: The duration of CHF was 64.7 ± 54.7 months and duration of LVAD support was prolonged (408 ± 455 days). MSTN PP levels in failing hearts were significantly higher than normal hearts (p=0.042) and significantly increased after LVAD support (p=0.021). Desmin, an intermediate filament in striated muscle, was significantly reduced after LVAD support (p=0.020), while MMP9, a matrix metalloproteinase central to extracellular matrix remodeling, was significantly increased in HF and after LVAD support (p=0.043, p=0.001, respectively). Actin, MHC SM, and fibrosis was elevated in failing hearts but was unchanged with LVAD support. Significant fibrosis was present in failing samples but remained unchanged despite LVAD support (0.33 ± 0.07 vs. 0.31 ± 0.12 arbitrary units, p=0.29).

    Conclusions: Persistent activation of myostatin after prolonged LVAD support is associated with worsened markers of cardiac muscle structural integrity. Further study is needed to define the optimal duration of mechanical assistance in patients with HF.


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