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 journalArticle

Abstract

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
Volume170
Issue number2
DOIs
StatePublished - Feb 2007
Externally publishedYes

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Skeletal Muscle
Heart Failure
Phenotype
Muscles
Calsequestrin
Sarcomeres
Cachexia
Peroxisome Proliferator-Activated Receptors
Muscular Atrophy
Skeletal Muscle Fibers
Quadriceps Muscle
Electron Transport Complex IV
Running
Transgenic Mice
Body Weight
Weights and Measures
Lung
Messenger RNA
Proteins

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Oxidative phenotype protects myofibers from pathological insults induced by chronic heart failure in mice. / Li, Ping; Waters, Richard E.; Redfern, Shelley I.; Zhang, Mei; Mao, Lan; Annex, Brian H.; Yan, Zhen.

In: American Journal of Pathology, Vol. 170, No. 2, 02.2007, p. 599-608.

Research output: Contribution to journalArticle

Li, Ping ; Waters, Richard E. ; Redfern, Shelley I. ; Zhang, Mei ; Mao, Lan ; Annex, Brian H. ; Yan, Zhen. / Oxidative phenotype protects myofibers from pathological insults induced by chronic heart failure in mice. In: American Journal of Pathology. 2007 ; Vol. 170, No. 2. pp. 599-608.
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