Cardiac myostatin upregulation occurs immediately after myocardial ischemia and is involved in skeletal muscle activation of atrophy

Biochem Biophys Res Commun. 2015 Jan 30;457(1):106-11. doi: 10.1016/j.bbrc.2014.12.057. Epub 2014 Dec 18.


Myostatin (MSTN), a negative regulator of muscle growth and size, is increased after acute myocardial infarction (AMI) but timing of upregulation after injury is not known. In this study, we investigated the timing of the MSTN/AKT/p38 pathway activation in heart and skeletal muscle after AMI, as well as the potential effect of cardiac injury-related MSTN endocrine signaling on skeletal muscle and other circulating growth factors.

Methods: Coronary artery ligation was performed in C57BL/6 mice at age 8 weeks to induce AMI. Mice were sacrificed at different time points (10 m, 1 h, 2 h, 6 h, 12 h, 24 h, 1 week, 2 weeks, 1 months and 2 months) after surgery (n=3 per time point, n=18 total).

Results: Cardiac and circulating MSTN upregulation occurred as early as 10 min after AMI. Two months after AMI, increased cardiac MSTN/SMAD2,3 and p38 together with decreased IGF-1/AKT signaling suggest an anti-hypertrophic profile. In skeletal muscle, an absence of local MSTN increase was accompanied by increased MSTN-dependent SMAD2,3 signaling, suggestive of paracrine effects due to cardiac-derived MSTN. Protein degradation by the ubiquitin-proteasome system in the skeletal muscle was also evident. Serum from 24h post-MI mice effectively induced a MSTN-dependent increase in atrogin1 and MuRF1.

Conclusion: Our study shows that cardiac MTSN activation occurs rapidly after cardiac ischemia and may be involved in peripheral protein degradation in the skeletal muscle by activating atrogin1 and MuRF1.

Keywords: Cardiac cachexia; Grow factors; Heart failure; Ischemia; Myostatin.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Male
  • Mice, Inbred C57BL
  • Muscle Proteins / metabolism
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • Muscular Atrophy / metabolism*
  • Muscular Atrophy / pathology
  • Myocardial Ischemia / blood
  • Myocardial Ischemia / pathology*
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Myostatin / blood
  • Myostatin / metabolism*
  • SKP Cullin F-Box Protein Ligases / metabolism
  • Signal Transduction
  • Smad Proteins / metabolism
  • Time Factors
  • Tripartite Motif Proteins
  • Ubiquitin-Protein Ligases / metabolism
  • Up-Regulation*


  • Biomarkers
  • Mstn protein, mouse
  • Muscle Proteins
  • Myostatin
  • Smad Proteins
  • Tripartite Motif Proteins
  • Fbxo32 protein, mouse
  • SKP Cullin F-Box Protein Ligases
  • Trim63 protein, mouse
  • Ubiquitin-Protein Ligases