Myostatin Is Elevated in Congenital Heart Disease and After Mechanical Unloading

Date

2011-09-13

Authors

Bish, Lawrence T.
George, Isaac
Maybaum, Simon
Yang, Jonathan
Chen, Jonathan M.
Sweeney, H. Lee

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Journal ISSN

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Abstract

Background: Myostatin is a negative regulator of skeletal muscle mass whose activity is upregulated in adult heart failure (HF); however, its role in congenital heart disease (CHD) is unknown.


Methods: We studied myostatin and IGF-1 expression via Western blot in cardiac tissue at varying degrees of myocardial dysfunction and after biventricular support in CHD by collecting myocardial biopsies from four patient cohorts: A) adult subjects with no known cardiopulmonary disease (left ventricle, LV), (Adult Normal), (n = 5); B) pediatric subjects undergoing congenital cardiac surgery with normal RV size and function (right ventricular outflow tract, RVOT), (n = 3); C) pediatric subjects with worsening but hemodynamically stable LV failure [LV and right ventricle (LV, RV,)] with biopsy collected at the time of orthotopic heart transplant (OHT), (n = 7); and D) pediatric subjects with decompensated bi-ventricular failure on BiVAD support with biopsy collected at OHT (LV, RV, BiVAD), (n = 3).


Results: The duration of HF was longest in OHT patients compared to BIVAD. The duration of BiVAD support was 4.361.9 days. Myostatin expression was significantly increased in LV-OHT compared to RV-OHT and RVOT, and was increased more than double in decompensated biventricular HF (BiVAD) compared to both OHT and RVOT. An increased myostatin/IGF-1 ratio was associated with ventricular dysfunction.


Conclusions: Myostatin expression in increased in CHD, and the myostatin/IGF-1 ratio increases as ventricular function deteriorates. Future investigation is necessary to determine if restoration of the physiologic myostatin/IGF-1 ratio has therapeutic potential in HF.

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Keywords

Research Article, Biology, Biochemistry, Proteins, Growth Factors, Genetics, Gene Expression, Molecular Cell Biology, Cell Growth, Medicine, Cardiovascular, Cardiomyopathies, Congenital Heart Disease, Heart Failure, Pediatric Cardiology, Surgery, Cardiovascular Surgery, Pediatric Surgery

Citation

PLoS One. 2011 Sep 13; 6(9):e23818