Apoptosis and changes in contractile protein pattern in the skeletal muscle in heart failure

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Analysis of Cardiac Contractile Dysfunction and Ca2+ Transients in Rodent Myocytes
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Analysis of Cardiac Contractile Dysfunction and Ca2+ Transients in Rodent Myocytes

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G Vescovo1, G B Ambrosio, L Dalla Libera

  • 1Divisione Medica, Ospedale di Adria (Ro), Italy.

Acta Physiologica Scandinavica
|June 20, 2001
PubMed

Insights

Chronic heart failure (CHF) reduces exercise capacity due to skeletal muscle atrophy and myosin heavy chain (MHC) shifts. Treatments targeting these factors may improve patient outcomes.

Area of Science:

  • Cardiology
  • Skeletal Muscle Physiology
  • Molecular Biology

Background:

  • Chronic heart failure (CHF) significantly impairs exercise capacity.
  • Reduced exercise capacity in CHF is linked to skeletal muscle changes, including atrophy and myosin heavy chain (MHC) shifts.
  • Skeletal muscle apoptosis is increasingly recognized as a contributor to CHF pathophysiology.

Purpose of the Study:

  • To investigate the relationship between skeletal muscle apoptosis, MHC composition, and exercise intolerance in CHF.
  • To explore the role of TNFalpha and sphingolipids in CHF-induced skeletal muscle apoptosis.
  • To evaluate the efficacy of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) in preventing these detrimental changes.

Main Methods:

  • Utilized a monocrotaline-induced rat model of right-sided heart failure.
  • Analyzed skeletal muscle apoptosis, MHC expression, and circulating TNFalpha and sphingosine levels in rats and CHF patients.
  • Correlated exercise capacity, muscle atrophy, and MHC composition with CHF severity.

Main Results:

  • CHF severity correlated positively with skeletal muscle apoptosis and circulating sphingosine levels.
  • Increased skeletal muscle apoptosis was associated with muscle atrophy and exercise limitation in CHF patients.
  • A shift towards 'fast' MHC isoforms in skeletal muscle correlated with CHF severity and premature muscle fatigue.
  • ACE inhibitors and ARBs demonstrated a preventative effect on MHC shifts and apoptosis.

Conclusions:

  • Skeletal muscle apoptosis and altered MHC composition are key contributors to exercise intolerance in CHF.
  • TNFalpha and sphingolipids may mediate CHF-related skeletal muscle apoptosis.
  • ACEi and ARBs show potential for mitigating skeletal muscle pathology in CHF, improving exercise capacity.

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