Oxidative phenotype protects myofibers from pathological insults induced by chronic heart failure in mice

Ping Li, Richard E. Waters, Shelley I. Redfern, Mei Zhang, Lan Mao, Brian H. Annex, Zhen Yan

Research output: Contribution to journalArticlepeer-review

80 Scopus citations


The fiber specificity of skeletal muscle abnormalities in chronic heart failure (CHF) has not been defined. We show here that transgenic mice (8 weeks old) with cardiac-specific overexpression of calsequestrin developed CHF (50.9% decrease in fractional shortening and 56.4% increase in lung weight, P < 0.001), cachexia (37.8% decrease in body weight, P < 0.001), and exercise intolerance (69.3% decrease in running distance to exhaustion, P < 0.001) without a significant change in muscle fiber-type composition. Slow oxidative soleus muscle maintained muscle mass, whereas fast glycolytic tibialis anterior and plantaris muscles underwent atrophy (11.6 and 13.3%, respectively; P < 0.05). In plantaris muscle, glycolytic type IId/x and IIb, but not oxidative type I and IIa, fibers displayed significant decreases in cross-sectional area (20.3%, P < 0.05). Fast glycolytic white vastus lateralis muscle showed sarcomere degeneration and decreased cytochrome c oxidase IV (39-5%, P < 0.01) and peroxisome proliferator-activated receptor γ coactivator 1α protein expression (30.3%, P < 0.01) along with a dramatic induction of the MAFbx/Atrogin-1 mRNA. These findings suggest that exercise intolerance can occur in CHF without fiber type switching in skeletal muscle and that oxidative phenotype renders myofibers resistant to pathological insults induced by CHF.

Original languageEnglish (US)
Pages (from-to)599-608
Number of pages10
JournalAmerican Journal of Pathology
Issue number2
StatePublished - Feb 2007
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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