Altered expression of myosin heavy chain in human skeletal muscle in chronic heart failure

Area of Science:

• Cardiology
• Skeletal Muscle Physiology
• Biochemistry

Background:

• Skeletal muscle alterations are observed in chronic heart failure (CHF).
• Myosin heavy chain (MHC) isoforms are key determinants of muscle fiber function.
• Understanding MHC isoform changes in CHF is crucial for comprehending exercise intolerance.

Purpose of the Study:

• To investigate alterations in MHC isoform composition in the vastus lateralis skeletal muscle of patients with CHF.
• To correlate MHC isoform expression with exercise capacity (peak oxygen consumption).

Main Methods:

• Biopsies of vastus lateralis muscle were obtained from nine male patients with class II-III CHF and nine age-matched healthy males.
• Relative content of MHC isoforms (I, IIa, IIx) was quantified using gel electrophoresis.
• Expression levels were compared between CHF patients and normal controls.

Main Results:

• CHF patients exhibited significantly lower relative content of MHC type I compared to normal controls (24% vs 48.4%).
• CHF patients showed a higher relative content of MHC type IIx than normal controls (20% vs 6.5%).
• No significant difference was found in MHC type IIa content between groups.
• Three out of nine CHF patients had undetectable MHC type I.
• Relative MHC type I expression in CHF patients correlated positively with peak oxygen consumption (r=0.70).

Conclusions:

• Significant alterations in MHC isoform expression, specifically a reduction in MHC type I and an increase in MHC type IIx, are present in skeletal muscle of CHF patients.
• These changes suggest a potential specific skeletal muscle myopathy in CHF, not solely attributable to deconditioning.
• MHC isoform alterations may contribute to impaired skeletal muscle contractile function and reduced exercise performance in CHF.