Abstract
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.
Highlights
The transcriptional responses of angiogenic factors to the different exercise training protocols were examined as part of the adaptation process of skeletal muscles following those types of exercise in heart failure (HF) patients
The main findings of our study were that both HIIT and combined HIIT with strength training resulted in similar increases in the expression of angiogenesis-related factors in skeletal muscles of HF patients
This study provided information on the exercise training-induced molecular responses, as well as the correlational relationships of angiogenesis-related factors, which are plausibly involved in a network of biological processes associated with the adaptive alterations of skeletal muscle to exercise training in HF patients
Summary
Reduced exercise capacity, which is a hallmark of HF and has been associated with poor prognosis, cannot be fully explained by the decrease of left ventricular ejection fraction (LVEF) in these patients [2,3]. These observations further support the importance of muscle hypothesis in HF-related exercise intolerance [4,5]. Aerobic exercise, in the form of either continuous or even high-intensity-interval-training (HIIT), has been traditionally employed in the cardiac rehabilitation programs of HF patients [6,8], while in the last decade a combined aerobic with strength training appeared to gain ground, mainly due to the benefits towards skeletal muscle atrophy. Previous work from our group showed that 3 months of combined
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