title: Oxidative phenotype protects myofibers from pathological insults induced by chronic heart failure in mice.
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 gamma co-activator 1alpha 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.
authors.affiliation: Division of Cardiology, Department of Medicine, Duke University Medical Center, 4321 Medical Park Dr., Suite 200, Durham, NC 27704, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Richard E
authors.initials: RE
authors.lastname: Waters
authors.forename: Shelley I
authors.initials: SI
authors.lastname: Redfern
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
authors.forename: Lan
authors.initials: L
authors.lastname: Mao
authors.forename: Brian H
authors.initials: BH
authors.lastname: Annex
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yan
mesh_terms: D000818:Animals; D001284:Atrophy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002100:Cachexia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002155:Calsequestrin / Q000096:biosynthesis / Q000235:genetics; D003576:Electron Transport Complex IV / Q000096:biosynthesis; D006019:Glycolysis; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009124:Muscle Proteins / Q000096:biosynthesis; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000648:ultrastructure*; D009929:Organ Size; D010084:Oxidation-Reduction; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D044843:SKP Cullin F-Box Protein Ligases / Q000096:biosynthesis; D012518:Sarcomeres / Q000378:metabolism* / Q000648:ultrastructure*; D015534:Trans-Activators / Q000096:biosynthesis; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis
chemical_list: D002155:Calsequestrin; D009124:Muscle Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; D003576:Electron Transport Complex IV; C486691:Fbxo32 protein, mouse; D044843:SKP Cullin F-Box Protein Ligases; C499084:Trim63 protein, mouse; D044767:Ubiquitin-Protein Ligases