title: Myostatin is elevated in congenital heart disease and after mechanical unloading.
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 4.3±1.9 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.
authors.affiliation: Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America. bish@mail.med.upenn.edu
authors.forename: Lawrence T
authors.initials: LT
authors.lastname: Bish
authors.forename: Isaac
authors.initials: I
authors.lastname: George
authors.forename: Simon
authors.initials: S
authors.lastname: Maybaum
authors.forename: Jonathan
authors.initials: J
authors.lastname: Yang
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Chen
authors.forename: H Lee
authors.initials: HL
authors.lastname: Sweeney
mesh_terms: D000328:Adult; D002648:Child; D005260:Female; D005786:Gene Expression Regulation; D006331:Heart Diseases / Q000150:complications / Q000151:congenital* / Q000378:metabolism* / Q000601:surgery; D006353:Heart-Assist Devices; D006801:Humans; D007223:Infant; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D055595:Mechanical Phenomena; D018006:Myogenic Regulatory Factors / Q000378:metabolism; D055435:Myostatin / Q000378:metabolism*; D018487:Ventricular Dysfunction, Left / Q000150:complications
chemical_list: D018006:Myogenic Regulatory Factors; D055435:Myostatin; D007334:Insulin-Like Growth Factor I