Dataset Information

Skeletal muscle alterations in chronic heart failure: differential effects on quadriceps and diaphragm.

ABSTRACT:

Background

Chronic heart failure (CHF) results in limb and respiratory muscle weakness, which contributes to exercise intolerance and increased morbidity and mortality, yet the molecular mechanisms remain poorly understood. Therefore, we aimed to compare parameters of antioxidative capacity, energy metabolism, and catabolic/anabolic balance in diaphragm and quadriceps muscle in an animal model of CHF.

Methods

Ligation of the left anterior descending coronary artery (n?=?13) or sham operation (n?=?11) was performed on Wistar Kyoto rats. After 12?weeks, echocardiography and invasive determination of maximal rates of left ventricular (LV) pressure change were performed. Antioxidative and metabolic enzyme activities and expression of catabolic/anabolic markers were assessed in quadriceps and diaphragm muscle.

Results

Ligated rats developed CHF (i.e. severe LV dilatation, reduced LV ejection fraction, and impaired maximal rates of LV pressure change; P?ConclusionChronic heart failure induced divergent antioxidative and metabolic but similar catabolic responses between the diaphragm and quadriceps. Despite the quadriceps demonstrating significant impairments in CHF, apparent beneficial adaptations of an increased antioxidative capacity were induced in the diaphragm. Nevertheless, muscle ring finger 1 and proteasome activity (markers of protein degradation) were elevated and oxidative enzyme activity failed to increase in the diaphragm of CHF rats, which suggest that a myopathy is likely present in respiratory muscle in CHF, despite its constant activation.

SUBMITTER: Mangner N

PROVIDER: S-EPMC4670747 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Publications

Skeletal muscle alterations in chronic heart failure: differential effects on quadriceps and diaphragm.

Mangner Norman N Weikert Bettina B Bowen T Scott TS Sandri Marcus M Höllriegel Robert R Erbs Sandra S Hambrecht Rainer R Schuler Gerhard G Linke Axel A Gielen Stephan S Adams Volker V

Journal of cachexia, sarcopenia and muscle 20150430 4

<h4>Background</h4>Chronic heart failure (CHF) results in limb and respiratory muscle weakness, which contributes to exercise intolerance and increased morbidity and mortality, yet the molecular mechanisms remain poorly understood. Therefore, we aimed to compare parameters of antioxidative capacity, energy metabolism, and catabolic/anabolic balance in diaphragm and quadriceps muscle in an animal model of CHF.<h4>Methods</h4>Ligation of the left anterior descending coronary artery (n = 13) or sha ...[more]

PMID: 26674018

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Project description:BackgroundExercise intolerance is a cardinal symptom in right (RV) and left ventricular (LV) failure. The underlying skeletal muscle contributes to increased morbidity in patients. Here, we compared skeletal muscle sarcopenia in a novel two-stage model of RV failure to an established model of LV failure.MethodsPulmonary artery banding (PAB) or aortic banding (AOB) was performed in weanling rats, inducing a transition from compensated cardiac hypertrophy (after 7 weeks) to heart failure (after 22-26 weeks). Cardiac function was characterized by echocardiography. Skeletal muscle catabolic/anabolic balance and energy metabolism were analysed by histological and biochemical methods, real-time PCR, and western blot.ResultsTwo clearly distinguishable stages of left or right heart disease with a comparable severity were reached. However, skeletal muscle impairment was significantly more pronounced in LV failure. While the compensatory stage resulted only in minor changes, soleus and gastrocnemius muscle of AOB rats at the decompensated stage demonstrated reduced weight and fibre diameter, higher proteasome activity and expression of the muscle-specific ubiquitin E3 ligases muscle-specific RING finger 1 and atrogin-1, increased expression of the atrophy marker myostatin, increased autophagy activation, and impaired mitochondrial function and respiratory chain gene expression. Soleus and gastrocnemius muscle of PAB rats did not show significant changes in muscle weight and proteasome or autophagy activation, but mitochondrial function was mildly impaired as well. The diaphragm did not demonstrate differences in any model or disease stage except for myostatin expression, which was altered at the decompensated stage in both models. Plasma interleukin (IL)-6 and angiotensin II were strongly increased at the decompensated stage (AOB > > PAB). Soleus and gastrocnemius muscle itself demonstrated an increase in IL-6 expression independent from blood-derived cytokines only in AOB animals. In vitro experiments in rat skeletal muscle cells suggested a direct impact of IL-6 and angiotensin II on distinctive atrophic changes.ConclusionsManifold skeletal muscle alterations are more pronounced in LV failure compared with RV failure despite a similar ventricular impairment. Most of the catabolic changes were observed in soleus or gastrocnemius muscle rather than in the constantly active diaphragm. Mitochondrial dysfunction and up-regulation of myostatin were identified as the earliest signs of skeletal muscle impairment.

Project description:Peripheral myopathy consists of a hallmark of heart failure (HF). Exercise enhanced skeletal muscle angiogenesis, and thus, it can be further beneficial towards the HF-induced myopathy. However, there is limited evidence regarding the exercise type that elicits optimum angiogenic responses of skeletal muscle in HF patients. This study aimed to (a) compare the effects of a high-intensity-interval-training (HIIT) or combined HIIT with strength training (COM) exercise protocol on the expression of angiogenesis-related factors in skeletal muscle of HF patients, and (b) examine the potential associations between the expression of those genes and capillarization in the trained muscles. Thirteen male patients with chronic HF (age: 51 ± 13 y; BMI: 27 ± 4 kg/m2) were randomly assigned to a 3-month exercise program that consisted of either HIIT (N = 6) or COM training (N = 7). Vastus lateralis muscle biopsies were performed pre- and post-training. RT-PCR was used to quantify the fold changes in mRNA expression of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGFR-2), hypoxia-inducible factor 1 alpha (HIF-1α), angiopoietin 1 (Ang-1), angiopoietin 2 (Ang-2), angiopoietin receptor (Tie2), and matrix metallopeptidase 9 (MMP-9), and immunohistochemistry to assess capillarization in skeletal muscle post-training. There was an overall increase in the expression levels of VEGF, VEGFR-2, HIF-1α, Ang2, and MMP9 post-training, while these changes were not different among groups. Changes in capillary-to-fibre ratio were found to be strongly associated with Tie2 and HIF-1α expression. This was the first study demonstrating that both HIIT and combined HIIT with strength training enhanced similarly the expression profile of angiogenic factors in skeletal muscle of HF patients, possibly driving the angiogenic program in the trained muscles, although those gene expression increases were found to be only partially related with muscle capillarization.

Dataset Information

Skeletal muscle alterations in chronic heart failure: differential effects on quadriceps and diaphragm.

Background

Methods

Results

Publications

Skeletal muscle alterations in chronic heart failure: differential effects on quadriceps and diaphragm.

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