Cargando…

Ubiquitin‐proteasome‐system and enzymes of energy metabolism in skeletal muscle of patients with HFpEF and HFrEF

BACKGROUND: Skeletal muscle (SM) alterations contribute to exercise intolerance in heart failure patients with preserved (HFpEF) or reduced (HFrEF) left ventricular ejection fraction (LVEF). Protein degradation via the ubiquitin‐proteasome‐system (UPS), nuclear apoptosis, and reduced mitochondrial e...

Descripción completa

Detalles Bibliográficos
Autores principales: Adams, Volker, Wunderlich, Sebastian, Mangner, Norman, Hommel, Jennifer, Esefeld, Katrin, Gielen, Stephan, Halle, Martin, Ellingsen, Øyvind, Van Craenenbroeck, Emeline M., Wisløff, Ulrik, Pieske, Burkert, Linke, Axel, Winzer, Ephraim B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318515/
https://www.ncbi.nlm.nih.gov/pubmed/33955206
http://dx.doi.org/10.1002/ehf2.13405
_version_ 1783730262501228544
author Adams, Volker
Wunderlich, Sebastian
Mangner, Norman
Hommel, Jennifer
Esefeld, Katrin
Gielen, Stephan
Halle, Martin
Ellingsen, Øyvind
Van Craenenbroeck, Emeline M.
Wisløff, Ulrik
Pieske, Burkert
Linke, Axel
Winzer, Ephraim B.
author_facet Adams, Volker
Wunderlich, Sebastian
Mangner, Norman
Hommel, Jennifer
Esefeld, Katrin
Gielen, Stephan
Halle, Martin
Ellingsen, Øyvind
Van Craenenbroeck, Emeline M.
Wisløff, Ulrik
Pieske, Burkert
Linke, Axel
Winzer, Ephraim B.
author_sort Adams, Volker
collection PubMed
description BACKGROUND: Skeletal muscle (SM) alterations contribute to exercise intolerance in heart failure patients with preserved (HFpEF) or reduced (HFrEF) left ventricular ejection fraction (LVEF). Protein degradation via the ubiquitin‐proteasome‐system (UPS), nuclear apoptosis, and reduced mitochondrial energy supply is associated with SM weakness in HFrEF. These mechanisms are incompletely studied in HFpEF, and a direct comparison between these groups is missing. METHODS AND RESULTS: Patients with HFpEF (LVEF ≥ 50%, septal E/e′ > 15 or >8 and NT‐proBNP > 220 pg/mL, n = 20), HFrEF (LVEF ≤ 35%, n = 20) and sedentary control subjects (Con, n = 12) were studied. Inflammatory markers were measured in serum, and markers of the UPS, nuclear apoptosis, and energy metabolism were determined in percutaneous SM biopsies. Both HFpEF and HFrEF showed increased proteolysis (MuRF‐1 protein expression, ubiquitination, and proteasome activity) with proteasome activity significantly related to interleukin‐6. Proteolysis was more pronounced in patients with lower exercise capacity as indicated by peak oxygen uptake in per cent predicted below the median. Markers of apoptosis did not differ between groups. Mitochondrial energy supply was reduced in HFpEF and HFrEF (complex‐I activity: −31% and −53%; malate dehydrogenase activity: −20% and −29%; both P < 0.05 vs. Con). In contrast, short‐term energy supply via creatine kinase was increased in HFpEF but decreased in HFrEF (47% and −45%; P < 0.05 vs. Con). CONCLUSIONS: Similarly to HFrEF, skeletal muscle in HFpEF is characterized by increased proteolysis linked to systemic inflammation and reduced exercise capacity. Energy metabolism is disturbed in both groups; however, its regulation seems to be severity‐dependent.
format Online
Article
Text
id pubmed-8318515
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-83185152021-07-31 Ubiquitin‐proteasome‐system and enzymes of energy metabolism in skeletal muscle of patients with HFpEF and HFrEF Adams, Volker Wunderlich, Sebastian Mangner, Norman Hommel, Jennifer Esefeld, Katrin Gielen, Stephan Halle, Martin Ellingsen, Øyvind Van Craenenbroeck, Emeline M. Wisløff, Ulrik Pieske, Burkert Linke, Axel Winzer, Ephraim B. ESC Heart Fail Original Research Articles BACKGROUND: Skeletal muscle (SM) alterations contribute to exercise intolerance in heart failure patients with preserved (HFpEF) or reduced (HFrEF) left ventricular ejection fraction (LVEF). Protein degradation via the ubiquitin‐proteasome‐system (UPS), nuclear apoptosis, and reduced mitochondrial energy supply is associated with SM weakness in HFrEF. These mechanisms are incompletely studied in HFpEF, and a direct comparison between these groups is missing. METHODS AND RESULTS: Patients with HFpEF (LVEF ≥ 50%, septal E/e′ > 15 or >8 and NT‐proBNP > 220 pg/mL, n = 20), HFrEF (LVEF ≤ 35%, n = 20) and sedentary control subjects (Con, n = 12) were studied. Inflammatory markers were measured in serum, and markers of the UPS, nuclear apoptosis, and energy metabolism were determined in percutaneous SM biopsies. Both HFpEF and HFrEF showed increased proteolysis (MuRF‐1 protein expression, ubiquitination, and proteasome activity) with proteasome activity significantly related to interleukin‐6. Proteolysis was more pronounced in patients with lower exercise capacity as indicated by peak oxygen uptake in per cent predicted below the median. Markers of apoptosis did not differ between groups. Mitochondrial energy supply was reduced in HFpEF and HFrEF (complex‐I activity: −31% and −53%; malate dehydrogenase activity: −20% and −29%; both P < 0.05 vs. Con). In contrast, short‐term energy supply via creatine kinase was increased in HFpEF but decreased in HFrEF (47% and −45%; P < 0.05 vs. Con). CONCLUSIONS: Similarly to HFrEF, skeletal muscle in HFpEF is characterized by increased proteolysis linked to systemic inflammation and reduced exercise capacity. Energy metabolism is disturbed in both groups; however, its regulation seems to be severity‐dependent. John Wiley and Sons Inc. 2021-05-05 /pmc/articles/PMC8318515/ /pubmed/33955206 http://dx.doi.org/10.1002/ehf2.13405 Text en © 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Research Articles
Adams, Volker
Wunderlich, Sebastian
Mangner, Norman
Hommel, Jennifer
Esefeld, Katrin
Gielen, Stephan
Halle, Martin
Ellingsen, Øyvind
Van Craenenbroeck, Emeline M.
Wisløff, Ulrik
Pieske, Burkert
Linke, Axel
Winzer, Ephraim B.
Ubiquitin‐proteasome‐system and enzymes of energy metabolism in skeletal muscle of patients with HFpEF and HFrEF
title Ubiquitin‐proteasome‐system and enzymes of energy metabolism in skeletal muscle of patients with HFpEF and HFrEF
title_full Ubiquitin‐proteasome‐system and enzymes of energy metabolism in skeletal muscle of patients with HFpEF and HFrEF
title_fullStr Ubiquitin‐proteasome‐system and enzymes of energy metabolism in skeletal muscle of patients with HFpEF and HFrEF
title_full_unstemmed Ubiquitin‐proteasome‐system and enzymes of energy metabolism in skeletal muscle of patients with HFpEF and HFrEF
title_short Ubiquitin‐proteasome‐system and enzymes of energy metabolism in skeletal muscle of patients with HFpEF and HFrEF
title_sort ubiquitin‐proteasome‐system and enzymes of energy metabolism in skeletal muscle of patients with hfpef and hfref
topic Original Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318515/
https://www.ncbi.nlm.nih.gov/pubmed/33955206
http://dx.doi.org/10.1002/ehf2.13405
work_keys_str_mv AT adamsvolker ubiquitinproteasomesystemandenzymesofenergymetabolisminskeletalmuscleofpatientswithhfpefandhfref
AT wunderlichsebastian ubiquitinproteasomesystemandenzymesofenergymetabolisminskeletalmuscleofpatientswithhfpefandhfref
AT mangnernorman ubiquitinproteasomesystemandenzymesofenergymetabolisminskeletalmuscleofpatientswithhfpefandhfref
AT hommeljennifer ubiquitinproteasomesystemandenzymesofenergymetabolisminskeletalmuscleofpatientswithhfpefandhfref
AT esefeldkatrin ubiquitinproteasomesystemandenzymesofenergymetabolisminskeletalmuscleofpatientswithhfpefandhfref
AT gielenstephan ubiquitinproteasomesystemandenzymesofenergymetabolisminskeletalmuscleofpatientswithhfpefandhfref
AT hallemartin ubiquitinproteasomesystemandenzymesofenergymetabolisminskeletalmuscleofpatientswithhfpefandhfref
AT ellingsenøyvind ubiquitinproteasomesystemandenzymesofenergymetabolisminskeletalmuscleofpatientswithhfpefandhfref
AT vancraenenbroeckemelinem ubiquitinproteasomesystemandenzymesofenergymetabolisminskeletalmuscleofpatientswithhfpefandhfref
AT wisløffulrik ubiquitinproteasomesystemandenzymesofenergymetabolisminskeletalmuscleofpatientswithhfpefandhfref
AT pieskeburkert ubiquitinproteasomesystemandenzymesofenergymetabolisminskeletalmuscleofpatientswithhfpefandhfref
AT linkeaxel ubiquitinproteasomesystemandenzymesofenergymetabolisminskeletalmuscleofpatientswithhfpefandhfref
AT winzerephraimb ubiquitinproteasomesystemandenzymesofenergymetabolisminskeletalmuscleofpatientswithhfpefandhfref