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Manifested skeletal muscle abnormalities in fast‐twitch, glycolytic myofibers in mice of chronic heart failure
Author(s) -
Li Ping,
Waters Richard E.,
Odronic Shelley I.,
Mao Lan,
Annex Brian H.,
Yan Zhen
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a387-a
Subject(s) - skeletal muscle , medicine , endocrinology , calsequestrin , soleus muscle , exercise intolerance , heart failure , mitochondrion , chemistry , ryanodine receptor , receptor , biochemistry
Exercise intolerance in chronic heart failure (CHF) is determined in part by the pathology in skeletal muscles. The mechanisms underlying this clinical syndrome are not well understood. We have characterized skeletal muscle abnormalities in a mouse CHF model with cardiac‐specific over‐expression of calsequestrin (CSQ). Compared with the wild type littermates, male CSQ mice (7–8 weeks old) developed severe cardiac dysfunction (‐50.9% fractional shortening, P < 0.001; +57.7% lung weight, P < 0.001). Skeletal muscle abnormalities in CSQ mice were specific to fast‐twitch fibers as shown by electron microscopic evidence of disarray of contractile apparatus and abnormal morphology of mitochondria in fast‐twitch plantaris muscle along with decreased muscle mass (‐13.3%, P < 0.05), but not in slow‐twitch soleus muscle. CSQ mice had decreased cross‐sectional area of type IId/x+IIb fibers (‐20%, P < 0.05). Cytochrome c oxidase IV (‐39.5%, P < 0.01) and peroxisome proliferators‐activated receptor γ coactivator 1α protein (‐30.3%, P < 0.01) expression decreased in fast‐twitch white vastus lateralis muscle, not in soleus muscle. Capillary to fiber ratio in CSQ mice (‐13.5%, P < 0.01) along with decreased capillary contacting (‐18%, P < 0.05) around type IId/x+IIb fibers. We conclude that CHF results in manifested abnormalities in fast‐twitch, glycolytic fibers in skeletal muscle which may play a primary role in the development of exercise intolerance.γα