Apoptosis of skeletal muscle myofibers and interstitial cells in experimental heart failure

J Mol Cell Cardiol. 1998 Nov;30(11):2449-59. doi: 10.1006/jmcc.1998.0807.


Congestive heart failure (CHF) is characterized by a limb skeletal muscle myopathy with shift from the slow aerobic, fatigue resistant fibers, to the fast, anaerobic ones, and muscle bulk loss. Apoptosis (A) has been recently demonstrated to play a role in several cardiovascular diseases.

Aim of the study: we have investigated the role of A in the skeletal muscle of the hindlimbs in an experimental model of CHF.

Animals and methods: CHF was induced in 7 males 80-100 g Sprague-Dawley rats with 30 mg/kg monocrotaline. Five age and diet matched controls were also studied. The time course of A was also studied in additional animals at day 0, 17, 24 and 30 days.

Results: At day 27 the electrophoretic analysis of myosin heavy chains (MHCs) demonstrated in the CHF rats the occurrence of a myopathy, with disappearance of slow MHC1 in the Tibialis Anterior (TA), and a significant shift from the slow to the fast isoforms in the soleus and EDL. With in situ DNA nick-end labelling (TUNEL) we found in the TA of CHF animals a significantly higher number of TUNEL positive nuclei (0.43 +/- 0.24 v 0.08 +/- 0.02, P<0.02 and TUNEL positive myonuclei (0.031 +/- 0.012 v 0.0025 +/- 0.005, P<0.02). The time course of A showed a progressive rise in interstitial and myocyte A, accompanied by a drop in fibers cross-sectional area and muscle weight/body weight, that came out to be significant at 30 days. Western blot showed a lower expression of Bcl-2 at 27 days and a further drop at 30 days in the CHF rats. Double staining for TUNEL and antibody against anti-MHC2a and anti MHC2b + 2x showed that A occurs non-selectively in all the myofiber types. BetaANP and Right Ventricle Mass/Volume (RVM/V) correlated significantly with total apoptotic nuclei.

Conclusions: In CHF myofibers A can lead to muscle atrophy. Endothelial cells A may produce an imbalance in myofibres nutrition with relative ischemia that triggers the preferential synthesis of fast anaerobic myosin as an adaptive mechanism or alternatively induce myofibres death.

MeSH terms

  • Animals
  • Apoptosis*
  • Connective Tissue Cells / pathology
  • Heart Failure / metabolism
  • Heart Failure / pathology*
  • In Situ Nick-End Labeling
  • Male
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology*
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • bcl-2-Associated X Protein


  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein