title: Skeletal muscle mitochondrial density, gene expression, and enzyme activities in human heart failure: minimal effects of the disease and resistance training.
abstract: Impaired skeletal muscle energetics could adversely affect physical and metabolic function in patients with heart failure (HF). The effect of HF on aspects of mitochondrial structure and function, independent of muscle disuse and other disease-related confounding factors, however, is unclear. Moreover, no study has evaluated whether resistance exercise training, a modality that increases functional capacity, might derive its benefits through modulation of mitochondrial structure and function. Thirteen HF patients and 14 age- and physical activity-matched controls were evaluated for skeletal muscle mitochondrial size/content, gene expression, and enzyme activity before and after an 18-wk resistance exercise-training program. At baseline, HF patients and controls had similar mitochondrial fractional areas, although HF patients had larger average mitochondrion size (P < 0.05) and a trend toward a reduced number of mitochondria (P ≤ 0.10). No differences in the expression of transcriptional regulators or cytochrome oxidase subunits or the activity of mitochondrial and cytosolic enzymes were noted. Relationships among transcriptional regulators suggested that networks controlling mitochondrial content and gene expression are intact. Resistance training increased (P < 0.01) mitochondrial transcription factor A expression in patients and controls, and this increase was related to improvements in muscle strength (P = 0.05). Training did not, however, alter mitochondrial size/content, enzyme activities, or expression of other transcriptional regulators. In conclusion, our results suggest that the HF syndrome has minimal effects on skeletal muscle mitochondrial biology when the confounding effects of muscle disuse and other disease-related factors are removed. Moreover, the beneficial effects of resistance training on physical function in HF patients and controls are likely not related to alterations in mitochondrial biology.
authors.affiliation: Department of Medicine, College of Medicine, University of Vermont, Burlington, VT, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Toth
authors.forename: Mark S
authors.initials: MS
authors.lastname: Miller
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Ward
authors.forename: Philip A
authors.initials: PA
authors.lastname: Ades
mesh_terms: D000368:Aged; D004789:Enzyme Activation / Q000235:genetics; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006333:Heart Failure / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D006801:Humans; D008297:Male; D008929:Mitochondria, Heart / Q000201:enzymology / Q000235:genetics; D008931:Mitochondria, Muscle / Q000201:enzymology* / Q000235:genetics; D053580:Muscle Strength / Q000235:genetics / Q000502:physiology; D018482:Muscle, Skeletal / Q000201:enzymology*; D010101:Oxygen Consumption / Q000235:genetics; D055070:Resistance Training / Q000009:adverse effects / Q000379:methods