IMR Press / RCM / Volume 24 / Issue 2 / DOI: 10.31083/j.rcm2402046
Open Access Original Research
Inflammation- and Tissue Remodeling-Related Gene Responses in Skeletal Muscle of Heart Failure Patients Following High-Intensity Interval Training
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1 Department of Life Science, European University Cyprus, 2404 Nicosia, Cyprus
2 Department of Physiology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
3 Clinical Ergospirometry, Exercise & Rehabilitation Laboratory, Evaggelismos Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece
*Correspondence: tfilipou@med.uoa.gr (Anastassios Philippou)
These authors contributed equally.
Rev. Cardiovasc. Med. 2023, 24(2), 46; https://doi.org/10.31083/j.rcm2402046
Submitted: 30 June 2022 | Revised: 2 November 2022 | Accepted: 19 December 2022 | Published: 6 February 2023
(This article belongs to the Special Issue Cardiac Rehabilitation—Volume 2)
Copyright: © 2023 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
Abstract

Background: Peripheral myopathy consists a hallmark of heart failure (HF) and has been associated with poor prognosis. Inflammation has been suggested to dominate this pathology, while exercise training is typically associated with the induction of anti-inflammatory mechanisms. However, the current knowledge regarding the involvement of inflammation-related genes in the exercise training-induced muscle adaptations in HF patients is very limited. Given that high-intensity interval training (HIIT) alone or combined with strength training (COM) has gained ground in HF cardiac rehabilitation, this study aimed to investigate the local muscle expression of inflammatory and tissue remodeling factors in HF patients, who underwent 3 months of these training schemes. In addition, we examined whether these exercise training-induced gene expression responses are associated with changes in exercise capacity in those patients. Methods: Thirteen male patients with chronic HF (age: 51 ± 13 y; body mass index (BMI): 27 ± 4 kg/m2) were randomly assigned to a 3-month exercise program consisted of either HIIT (N = 6) or COM training (N = 7). Muscle tissue biopsies were obtained from vastus lateralis pre- and post-training and transcriptional changes in interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factor-1 alpha (TNF-1α), urokinase-type plasminogen activator (uPA), urokinase-type plasminogen activator receptor (uPAR), and transforming growth factor-beta 1 (TGF-β1) were quantified by RT-PCR. Results: An overall increase in the expression levels of selected inflammatory (IL-8, TNF-1α) and remodeling factors (uPAR) was found post-training (p < 0.05), while IL-6, uPA and TGF-β1 gene expression remained unchanged (p > 0.05). The observed alterations did not differ between training groups. Additionally, IL-8 changes were found to be correlated with the improvement in exercise capacity post-training (p < 0.05). Conclusions: This is the first study demonstrating an increase in intramuscular inflammatory and remodeling key factors induced by HIIT or COM training in HF patients. Combining these observations with our previous findings of improved muscle hypertrophy and capillarization post-training in these patients, the findings of the present study may suggest that inflammatory responses are part of an ongoing remodeling process in the exercising skeletal muscle. Clinical Trial Registration: NCT02387411.

Keywords
heart failure
cardiac rehabilitation
inflammation
skeletal muscle remodelling
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