Heart failure (HF) is characterized by a skeletal muscle
myopathy with increased expression of fast
myosin heavy chains (MHCs). The skeletal muscle-specific molecular regulatory mechanisms controlling MHC expression during HF have not been described.
Myogenic regulatory factors (MRFs), a family of transcriptional factors that control the expression of several skeletal muscle-specific genes, may be related to these alterations. This investigation was undertaken in order to examine potential relationships between MRF
mRNA expression and MHC
protein isoforms in Wistar rat skeletal muscle with
monocrotaline-induced HF. We studied soleus (
Sol) and extensor digitorum longus (EDL) muscles from both HF and control Wistar rats. MyoD,
myogenin and
MRF4 contents were determined using reverse transcription-polymerase chain reaction while MHC
isoforms were separated using
polyacrylamide gel electrophoresis. Despite no change in MHC composition of Wistar rat skeletal muscles with HF, the
mRNA relative expression of MyoD in
Sol and EDL muscles and that of
MRF4 in
Sol muscle were significantly reduced, whereas
myogenin was not changed in both muscles. This down-regulation in the
mRNA relative expression of
MRF4 in
Sol was associated with
atrophy in response to HF while these alterations were not present in EDL muscle. Taken together, our results show a potential role for MRFs in skeletal muscle
myopathy during HF.