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Effects of homoarginine supplementation on heart and skeletal muscle of rats with heart failure with preserved ejection fraction

AIM: Heart failure with preserved ejection fraction (HFpEF) is associated with left ventricular stiffness, impaired diastolic relaxation, and severe exercise intolerance. Decreased homoarginine (hArg) levels are an independent predictor of mortality in cardiovascular disease and correlate with impai...

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Autores principales: Büttner, Petra, Adams, Volker, Werner, Sarah, Ossmann, Susann, Besler, Christian, Schwedhelm, Edzard, Thiele, Holger
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9773648/
https://www.ncbi.nlm.nih.gov/pubmed/36043453
http://dx.doi.org/10.1002/ehf2.14110
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author Büttner, Petra
Adams, Volker
Werner, Sarah
Ossmann, Susann
Besler, Christian
Schwedhelm, Edzard
Thiele, Holger
author_facet Büttner, Petra
Adams, Volker
Werner, Sarah
Ossmann, Susann
Besler, Christian
Schwedhelm, Edzard
Thiele, Holger
author_sort Büttner, Petra
collection PubMed
description AIM: Heart failure with preserved ejection fraction (HFpEF) is associated with left ventricular stiffness, impaired diastolic relaxation, and severe exercise intolerance. Decreased homoarginine (hArg) levels are an independent predictor of mortality in cardiovascular disease and correlate with impaired exercise performance. We recently reported alterations in arginine, hArg, and related amino acids in obese ZSF1 rats (O‐ZSF1), with a HFpEF phenotype. Although low hArg is associated with diastolic dysfunction in humans, potential effects of hArg supplementation were not tested yet. METHODS AND RESULTS: At an age of 6 weeks, 12 O‐ZSF1 were randomized into two groups: (1) O‐ZSF1 rats supplemented with hArg in their drinking water (sO‐ZSF1) or (2) O‐ZSF1 rats receiving no hArg supplementation (O‐ZSF1). At an age of 32 weeks, effects of primary prevention by hArg supplementation on echocardiographic, histological, and functional parameters of heart and skeletal muscle were determined. Lean ZSF1 rats (L‐ZSF1) served as controls. hArg supplementation did not prevent impairment of diastolic relaxation (E/e′: O‐ZSF1 21 ± 3 vs. sO‐ZSF1 22 ± 3, P = 0.954, L‐ZSF1 18 ± 5) but resulted in more cardiac fibrosis (histological collagen staining: +57% in sO‐ZSF1 vs. O‐ZSF1, P = 0.027) and increased collagen gene expression (Col1a1: +48% in sO‐ZSF1 vs. O‐ZSF1, P = 0.026). In contrary, right ventricular function was preserved by hArg supplementation (TAPSE (mm): O‐ZSF1 1.2 ± 0.3 vs. sO‐ZSF1 1.7 ± 0.3, P = 0.020, L‐ZSF1 1.8 ± 0.4). Musculus soleus maximal specific muscle force (N/cm(2)) in O‐ZSF1 (30.4 ± 0.8) and sO‐ZSF1 (31.9 ± 0.9) was comparable but significantly reduced compared with L‐ZSF1 (36.4 ± 0.7; both P < 0.05). Maximal absolute muscle force (g) (O‐ZSF1: 177.6 ± 7.8, sO‐ZSF1: 187.8 ± 5.0, L‐ZSF1: 181.5 ± 7.9, all P > 0.05) and cross‐sectional fibre area (arbitrary units) (O‐ZSF1: 1697 ± 57, sO‐ZSF1: 1965 ± 121, L‐ZSF1: 1691 ± 104, all P > 0.05) were not altered. CONCLUSIONS: Preservation of physiological hArg level in HFpEF may not be suited to prevent alterations in left ventricular and skeletal muscle function and structure. However, hArg supplementation may be beneficial for right ventricular function especially in pulmonary hypertension in HFpEF. We may speculate that clinically observed decreased hArg level are not the cause but the consequence of a yet unrecognized pathomechanism that underpins HFpEF.
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spelling pubmed-97736482022-12-23 Effects of homoarginine supplementation on heart and skeletal muscle of rats with heart failure with preserved ejection fraction Büttner, Petra Adams, Volker Werner, Sarah Ossmann, Susann Besler, Christian Schwedhelm, Edzard Thiele, Holger ESC Heart Fail Short Communications AIM: Heart failure with preserved ejection fraction (HFpEF) is associated with left ventricular stiffness, impaired diastolic relaxation, and severe exercise intolerance. Decreased homoarginine (hArg) levels are an independent predictor of mortality in cardiovascular disease and correlate with impaired exercise performance. We recently reported alterations in arginine, hArg, and related amino acids in obese ZSF1 rats (O‐ZSF1), with a HFpEF phenotype. Although low hArg is associated with diastolic dysfunction in humans, potential effects of hArg supplementation were not tested yet. METHODS AND RESULTS: At an age of 6 weeks, 12 O‐ZSF1 were randomized into two groups: (1) O‐ZSF1 rats supplemented with hArg in their drinking water (sO‐ZSF1) or (2) O‐ZSF1 rats receiving no hArg supplementation (O‐ZSF1). At an age of 32 weeks, effects of primary prevention by hArg supplementation on echocardiographic, histological, and functional parameters of heart and skeletal muscle were determined. Lean ZSF1 rats (L‐ZSF1) served as controls. hArg supplementation did not prevent impairment of diastolic relaxation (E/e′: O‐ZSF1 21 ± 3 vs. sO‐ZSF1 22 ± 3, P = 0.954, L‐ZSF1 18 ± 5) but resulted in more cardiac fibrosis (histological collagen staining: +57% in sO‐ZSF1 vs. O‐ZSF1, P = 0.027) and increased collagen gene expression (Col1a1: +48% in sO‐ZSF1 vs. O‐ZSF1, P = 0.026). In contrary, right ventricular function was preserved by hArg supplementation (TAPSE (mm): O‐ZSF1 1.2 ± 0.3 vs. sO‐ZSF1 1.7 ± 0.3, P = 0.020, L‐ZSF1 1.8 ± 0.4). Musculus soleus maximal specific muscle force (N/cm(2)) in O‐ZSF1 (30.4 ± 0.8) and sO‐ZSF1 (31.9 ± 0.9) was comparable but significantly reduced compared with L‐ZSF1 (36.4 ± 0.7; both P < 0.05). Maximal absolute muscle force (g) (O‐ZSF1: 177.6 ± 7.8, sO‐ZSF1: 187.8 ± 5.0, L‐ZSF1: 181.5 ± 7.9, all P > 0.05) and cross‐sectional fibre area (arbitrary units) (O‐ZSF1: 1697 ± 57, sO‐ZSF1: 1965 ± 121, L‐ZSF1: 1691 ± 104, all P > 0.05) were not altered. CONCLUSIONS: Preservation of physiological hArg level in HFpEF may not be suited to prevent alterations in left ventricular and skeletal muscle function and structure. However, hArg supplementation may be beneficial for right ventricular function especially in pulmonary hypertension in HFpEF. We may speculate that clinically observed decreased hArg level are not the cause but the consequence of a yet unrecognized pathomechanism that underpins HFpEF. John Wiley and Sons Inc. 2022-08-31 /pmc/articles/PMC9773648/ /pubmed/36043453 http://dx.doi.org/10.1002/ehf2.14110 Text en © 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Short Communications
Büttner, Petra
Adams, Volker
Werner, Sarah
Ossmann, Susann
Besler, Christian
Schwedhelm, Edzard
Thiele, Holger
Effects of homoarginine supplementation on heart and skeletal muscle of rats with heart failure with preserved ejection fraction
title Effects of homoarginine supplementation on heart and skeletal muscle of rats with heart failure with preserved ejection fraction
title_full Effects of homoarginine supplementation on heart and skeletal muscle of rats with heart failure with preserved ejection fraction
title_fullStr Effects of homoarginine supplementation on heart and skeletal muscle of rats with heart failure with preserved ejection fraction
title_full_unstemmed Effects of homoarginine supplementation on heart and skeletal muscle of rats with heart failure with preserved ejection fraction
title_short Effects of homoarginine supplementation on heart and skeletal muscle of rats with heart failure with preserved ejection fraction
title_sort effects of homoarginine supplementation on heart and skeletal muscle of rats with heart failure with preserved ejection fraction
topic Short Communications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9773648/
https://www.ncbi.nlm.nih.gov/pubmed/36043453
http://dx.doi.org/10.1002/ehf2.14110
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