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Changes in skeletal muscle myosin heavy chain isoform content during congestive heart failure
Espen E Spangenburg1, Robert J Talmadge, Timothy I Musch
1Muscle Function Laboratory, Department of Human Nutrition, Foods and Exercise, Virginia Polytechnic Institute and State University, Blacksburg 24061, USA. spangenburge@missouri.edu
Insights
Congestive heart failure (CHF) alters skeletal muscle myosin heavy chain (MHC) expression, particularly in fast isoforms, with changes correlating to CHF severity. This suggests muscle-specific susceptibility and potential impact on exercise capacity.
Area of Science:
- Physiology
- Molecular Biology
- Cardiovascular Disease
Background:
- Congestive heart failure (CHF) is associated with reduced skeletal muscle function.
- Changes in contractile protein expression, specifically myosin heavy chain (MHC) isoforms, are implicated in muscle dysfunction during CHF.
Purpose of the Study:
- To investigate if skeletal muscles within the same functional group exhibit similar changes in MHC isoform expression during CHF.
- To determine the relationship between the magnitude of MHC alterations and the severity of CHF.
Main Methods:
- Utilized the rat coronary ligation model to induce mild and severe forms of CHF.
- Analyzed MHC isoform proportions in plantar flexor muscles (soleus, gastrocnemius, plantaris).
Main Results:
- Soleus and white gastrocnemius muscles showed no alterations in whole-muscle MHC isoform proportions.
- Red gastrocnemius muscle exhibited significant increases in fast MHC isoforms (MHC IIx and IIb).
- Plantaris muscle showed a significant increase in MHC type IIb at the expense of MHC type IIx.
- Many observed MHC isoform changes correlated significantly with indices of CHF severity.
Conclusions:
- Skeletal muscle MHC isoform expression is altered in a muscle-specific manner during CHF, with some muscles being more susceptible.
- The extent of these MHC alterations is related to the severity of CHF.
- These molecular changes in MHC isoforms may contribute to impaired skeletal muscle performance and reduced exercise capacity in CHF patients.
Abstract:
Recent investigations have suggested that changes in contractile protein expression contribute to reductions in skeletal muscle function during congestive heart failure (CHF). Myosin heavy chain (MHC), a major contractile protein, has been shown to undergo alterations in protein isoform expression during CHF. The purpose of this investigation was twofold: (1) to determine whether muscles of the same functional group undergo similar changes in MHC expression, and (2) determine whether the magnitude of alterations in MHC is related to the severity of CHF. Using the rat coronary ligation model, mild and severe forms of CHF were produced and muscles of the plantar flexor group were analyzed. Whole-muscle MHC isoform proportions were not altered in the soleus and white gastrocnemius muscle, however significant increases in the percentage of fast MHC isoforms (7-9% increases in MHC IIx and IIb expression) were found in the red gastrocnemius muscle. In addition, there were significant proportional increases (8%) in MHC type IIb at the expense of MHC type IIx in the plantaris muscle. Many of the changes in the proportions of MHC isoforms were significantly correlated with indices of CHF severity. This indicates that changes in skeletal muscle MHC isoform expression are related to the severity of CHF and suggests that some peripheral skeletal muscles are more susceptible to shifts in MHC expression due to CHF. These changes in MHC isoform expression may contribute to alterations in the physiological performance of skeletal muscle and exercise capacity during CHF.