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Effects of aerobic and inspiratory training on skeletal muscle microRNA‐1 and downstream‐associated pathways in patients with heart failure

BACKGROUND: The exercise intolerance in chronic heart failure with reduced ejection fraction (HFrEF) is mostly attributed to alterations in skeletal muscle. However, the mechanisms underlying the skeletal myopathy in patients with HFrEF are not completely understood. We hypothesized that (i) aerobic...

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Autores principales: Antunes‐Correa, Ligia M., Trevizan, Patricia F., Bacurau, Aline V.N., Ferreira‐Santos, Larissa, Gomes, João L.P., Urias, Ursula, Oliveira, Patricia A., Alves, Maria Janieire N.N., de Almeida, Dirceu R., Brum, Patricia C., Oliveira, Edilamar M., Hajjar, Ludhmila, Kalil Filho, Roberto, Negrão, Carlos Eduardo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7015255/
https://www.ncbi.nlm.nih.gov/pubmed/31743617
http://dx.doi.org/10.1002/jcsm.12495
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author Antunes‐Correa, Ligia M.
Trevizan, Patricia F.
Bacurau, Aline V.N.
Ferreira‐Santos, Larissa
Gomes, João L.P.
Urias, Ursula
Oliveira, Patricia A.
Alves, Maria Janieire N.N.
de Almeida, Dirceu R.
Brum, Patricia C.
Oliveira, Edilamar M.
Hajjar, Ludhmila
Kalil Filho, Roberto
Negrão, Carlos Eduardo
author_facet Antunes‐Correa, Ligia M.
Trevizan, Patricia F.
Bacurau, Aline V.N.
Ferreira‐Santos, Larissa
Gomes, João L.P.
Urias, Ursula
Oliveira, Patricia A.
Alves, Maria Janieire N.N.
de Almeida, Dirceu R.
Brum, Patricia C.
Oliveira, Edilamar M.
Hajjar, Ludhmila
Kalil Filho, Roberto
Negrão, Carlos Eduardo
author_sort Antunes‐Correa, Ligia M.
collection PubMed
description BACKGROUND: The exercise intolerance in chronic heart failure with reduced ejection fraction (HFrEF) is mostly attributed to alterations in skeletal muscle. However, the mechanisms underlying the skeletal myopathy in patients with HFrEF are not completely understood. We hypothesized that (i) aerobic exercise training (AET) and inspiratory muscle training (IMT) would change skeletal muscle microRNA‐1 expression and downstream‐associated pathways in patients with HFrEF and (ii) AET and IMT would increase leg blood flow (LBF), functional capacity, and quality of life in these patients. METHODS: Patients age 35 to 70 years, left ventricular ejection fraction (LVEF) ≤40%, New York Heart Association functional classes II–III, were randomized into control, IMT, and AET groups. Skeletal muscle changes were examined by vastus lateralis biopsy. LBF was measured by venous occlusion plethysmography, functional capacity by cardiopulmonary exercise test, and quality of life by Minnesota Living with Heart Failure Questionnaire. All patients were evaluated at baseline and after 4 months. RESULTS: Thirty‐three patients finished the study protocol: control (n = 10; LVEF = 25 ± 1%; six males), IMT (n = 11; LVEF = 31 ± 2%; three males), and AET (n = 12; LVEF = 26 ± 2%; seven males). AET, but not IMT, increased the expression of microRNA‐1 (P = 0.02; percent changes = 53 ± 17%), decreased the expression of PTEN (P = 0.003; percent changes = −15 ± 0.03%), and tended to increase the p‐AKT(ser473)/AKT ratio (P = 0.06). In addition, AET decreased HDAC4 expression (P = 0.03; percent changes = −40 ± 19%) and upregulated follistatin (P = 0.01; percent changes = 174 ± 58%), MEF2C (P = 0.05; percent changes = 34 ± 15%), and MyoD expression (P = 0.05; percent changes = 47 ± 18%). AET also increased muscle cross‐sectional area (P = 0.01). AET and IMT increased LBF, functional capacity, and quality of life. Further analyses showed a significant correlation between percent changes in microRNA‐1 and percent changes in follistatin mRNA (P = 0.001, rho = 0.58) and between percent changes in follistatin mRNA and percent changes in peak VO(2) (P = 0.004, rho = 0.51). CONCLUSIONS: AET upregulates microRNA‐1 levels and decreases the protein expression of PTEN, which reduces the inhibitory action on the PI3K‐AKT pathway that regulates the skeletal muscle tropism. The increased levels of microRNA‐1 also decreased HDAC4 and increased MEF2c, MyoD, and follistatin expression, improving skeletal muscle regeneration. These changes associated with the increase in muscle cross‐sectional area and LBF contribute to the attenuation in skeletal myopathy, and the improvement in functional capacity and quality of life in patients with HFrEF. IMT caused no changes in microRNA‐1 and in the downstream‐associated pathway. The increased functional capacity provoked by IMT seems to be associated with amelioration in the respiratory function instead of changes in skeletal muscle. http://ClinicalTrials.gov (Identifier: NCT01747395)
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spelling pubmed-70152552020-03-24 Effects of aerobic and inspiratory training on skeletal muscle microRNA‐1 and downstream‐associated pathways in patients with heart failure Antunes‐Correa, Ligia M. Trevizan, Patricia F. Bacurau, Aline V.N. Ferreira‐Santos, Larissa Gomes, João L.P. Urias, Ursula Oliveira, Patricia A. Alves, Maria Janieire N.N. de Almeida, Dirceu R. Brum, Patricia C. Oliveira, Edilamar M. Hajjar, Ludhmila Kalil Filho, Roberto Negrão, Carlos Eduardo J Cachexia Sarcopenia Muscle Original Articles BACKGROUND: The exercise intolerance in chronic heart failure with reduced ejection fraction (HFrEF) is mostly attributed to alterations in skeletal muscle. However, the mechanisms underlying the skeletal myopathy in patients with HFrEF are not completely understood. We hypothesized that (i) aerobic exercise training (AET) and inspiratory muscle training (IMT) would change skeletal muscle microRNA‐1 expression and downstream‐associated pathways in patients with HFrEF and (ii) AET and IMT would increase leg blood flow (LBF), functional capacity, and quality of life in these patients. METHODS: Patients age 35 to 70 years, left ventricular ejection fraction (LVEF) ≤40%, New York Heart Association functional classes II–III, were randomized into control, IMT, and AET groups. Skeletal muscle changes were examined by vastus lateralis biopsy. LBF was measured by venous occlusion plethysmography, functional capacity by cardiopulmonary exercise test, and quality of life by Minnesota Living with Heart Failure Questionnaire. All patients were evaluated at baseline and after 4 months. RESULTS: Thirty‐three patients finished the study protocol: control (n = 10; LVEF = 25 ± 1%; six males), IMT (n = 11; LVEF = 31 ± 2%; three males), and AET (n = 12; LVEF = 26 ± 2%; seven males). AET, but not IMT, increased the expression of microRNA‐1 (P = 0.02; percent changes = 53 ± 17%), decreased the expression of PTEN (P = 0.003; percent changes = −15 ± 0.03%), and tended to increase the p‐AKT(ser473)/AKT ratio (P = 0.06). In addition, AET decreased HDAC4 expression (P = 0.03; percent changes = −40 ± 19%) and upregulated follistatin (P = 0.01; percent changes = 174 ± 58%), MEF2C (P = 0.05; percent changes = 34 ± 15%), and MyoD expression (P = 0.05; percent changes = 47 ± 18%). AET also increased muscle cross‐sectional area (P = 0.01). AET and IMT increased LBF, functional capacity, and quality of life. Further analyses showed a significant correlation between percent changes in microRNA‐1 and percent changes in follistatin mRNA (P = 0.001, rho = 0.58) and between percent changes in follistatin mRNA and percent changes in peak VO(2) (P = 0.004, rho = 0.51). CONCLUSIONS: AET upregulates microRNA‐1 levels and decreases the protein expression of PTEN, which reduces the inhibitory action on the PI3K‐AKT pathway that regulates the skeletal muscle tropism. The increased levels of microRNA‐1 also decreased HDAC4 and increased MEF2c, MyoD, and follistatin expression, improving skeletal muscle regeneration. These changes associated with the increase in muscle cross‐sectional area and LBF contribute to the attenuation in skeletal myopathy, and the improvement in functional capacity and quality of life in patients with HFrEF. IMT caused no changes in microRNA‐1 and in the downstream‐associated pathway. The increased functional capacity provoked by IMT seems to be associated with amelioration in the respiratory function instead of changes in skeletal muscle. http://ClinicalTrials.gov (Identifier: NCT01747395) John Wiley and Sons Inc. 2019-11-19 2020-02 /pmc/articles/PMC7015255/ /pubmed/31743617 http://dx.doi.org/10.1002/jcsm.12495 Text en © 2019 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Antunes‐Correa, Ligia M.
Trevizan, Patricia F.
Bacurau, Aline V.N.
Ferreira‐Santos, Larissa
Gomes, João L.P.
Urias, Ursula
Oliveira, Patricia A.
Alves, Maria Janieire N.N.
de Almeida, Dirceu R.
Brum, Patricia C.
Oliveira, Edilamar M.
Hajjar, Ludhmila
Kalil Filho, Roberto
Negrão, Carlos Eduardo
Effects of aerobic and inspiratory training on skeletal muscle microRNA‐1 and downstream‐associated pathways in patients with heart failure
title Effects of aerobic and inspiratory training on skeletal muscle microRNA‐1 and downstream‐associated pathways in patients with heart failure
title_full Effects of aerobic and inspiratory training on skeletal muscle microRNA‐1 and downstream‐associated pathways in patients with heart failure
title_fullStr Effects of aerobic and inspiratory training on skeletal muscle microRNA‐1 and downstream‐associated pathways in patients with heart failure
title_full_unstemmed Effects of aerobic and inspiratory training on skeletal muscle microRNA‐1 and downstream‐associated pathways in patients with heart failure
title_short Effects of aerobic and inspiratory training on skeletal muscle microRNA‐1 and downstream‐associated pathways in patients with heart failure
title_sort effects of aerobic and inspiratory training on skeletal muscle microrna‐1 and downstream‐associated pathways in patients with heart failure
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7015255/
https://www.ncbi.nlm.nih.gov/pubmed/31743617
http://dx.doi.org/10.1002/jcsm.12495
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