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Statin-induced myopathic changes in primary human muscle cells and reversal by a prostaglandin F2 alpha analogue

Statin-related muscle side effects are a constant healthcare problem since patient compliance is dependent on side effects. Statins reduce plasma cholesterol levels and can prevent secondary cardiovascular diseases. Although statin-induced muscle damage has been studied, preventive or curative thera...

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Autores principales: Grunwald, Stefanie Anke, Popp, Oliver, Haafke, Stefanie, Jedraszczak, Nicole, Grieben, Ulrike, Saar, Kathrin, Patone, Giannino, Kress, Wolfram, Steinhagen-Thiessen, Elisabeth, Dittmar, Gunnar, Spuler, Simone
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005895/
https://www.ncbi.nlm.nih.gov/pubmed/32034223
http://dx.doi.org/10.1038/s41598-020-58668-2
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author Grunwald, Stefanie Anke
Popp, Oliver
Haafke, Stefanie
Jedraszczak, Nicole
Grieben, Ulrike
Saar, Kathrin
Patone, Giannino
Kress, Wolfram
Steinhagen-Thiessen, Elisabeth
Dittmar, Gunnar
Spuler, Simone
author_facet Grunwald, Stefanie Anke
Popp, Oliver
Haafke, Stefanie
Jedraszczak, Nicole
Grieben, Ulrike
Saar, Kathrin
Patone, Giannino
Kress, Wolfram
Steinhagen-Thiessen, Elisabeth
Dittmar, Gunnar
Spuler, Simone
author_sort Grunwald, Stefanie Anke
collection PubMed
description Statin-related muscle side effects are a constant healthcare problem since patient compliance is dependent on side effects. Statins reduce plasma cholesterol levels and can prevent secondary cardiovascular diseases. Although statin-induced muscle damage has been studied, preventive or curative therapies are yet to be reported. We exposed primary human muscle cell populations (n = 22) to a lipophilic (simvastatin) and a hydrophilic (rosuvastatin) statin and analyzed their expressome. Data and pathway analyses included GOrilla, Reactome and DAVID. We measured mevalonate intracellularly and analyzed eicosanoid profiles secreted by human muscle cells. Functional assays included proliferation and differentiation quantification. More than 1800 transcripts and 900 proteins were differentially expressed after exposure to statins. Simvastatin had a stronger effect on the expressome than rosuvastatin, but both statins influenced cholesterol biosynthesis, fatty acid metabolism, eicosanoid synthesis, proliferation, and differentiation of human muscle cells. Cultured human muscle cells secreted ω-3 and ω-6 derived eicosanoids and prostaglandins. The ω-6 derived metabolites were found at higher levels secreted from simvastatin-treated primary human muscle cells. Eicosanoids rescued muscle cell differentiation. Our data suggest a new aspect on the role of skeletal muscle in cholesterol metabolism. For clinical practice, the addition of omega-n fatty acids might be suitable to prevent or treat statin-myopathy.
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spelling pubmed-70058952020-02-18 Statin-induced myopathic changes in primary human muscle cells and reversal by a prostaglandin F2 alpha analogue Grunwald, Stefanie Anke Popp, Oliver Haafke, Stefanie Jedraszczak, Nicole Grieben, Ulrike Saar, Kathrin Patone, Giannino Kress, Wolfram Steinhagen-Thiessen, Elisabeth Dittmar, Gunnar Spuler, Simone Sci Rep Article Statin-related muscle side effects are a constant healthcare problem since patient compliance is dependent on side effects. Statins reduce plasma cholesterol levels and can prevent secondary cardiovascular diseases. Although statin-induced muscle damage has been studied, preventive or curative therapies are yet to be reported. We exposed primary human muscle cell populations (n = 22) to a lipophilic (simvastatin) and a hydrophilic (rosuvastatin) statin and analyzed their expressome. Data and pathway analyses included GOrilla, Reactome and DAVID. We measured mevalonate intracellularly and analyzed eicosanoid profiles secreted by human muscle cells. Functional assays included proliferation and differentiation quantification. More than 1800 transcripts and 900 proteins were differentially expressed after exposure to statins. Simvastatin had a stronger effect on the expressome than rosuvastatin, but both statins influenced cholesterol biosynthesis, fatty acid metabolism, eicosanoid synthesis, proliferation, and differentiation of human muscle cells. Cultured human muscle cells secreted ω-3 and ω-6 derived eicosanoids and prostaglandins. The ω-6 derived metabolites were found at higher levels secreted from simvastatin-treated primary human muscle cells. Eicosanoids rescued muscle cell differentiation. Our data suggest a new aspect on the role of skeletal muscle in cholesterol metabolism. For clinical practice, the addition of omega-n fatty acids might be suitable to prevent or treat statin-myopathy. Nature Publishing Group UK 2020-02-07 /pmc/articles/PMC7005895/ /pubmed/32034223 http://dx.doi.org/10.1038/s41598-020-58668-2 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Grunwald, Stefanie Anke
Popp, Oliver
Haafke, Stefanie
Jedraszczak, Nicole
Grieben, Ulrike
Saar, Kathrin
Patone, Giannino
Kress, Wolfram
Steinhagen-Thiessen, Elisabeth
Dittmar, Gunnar
Spuler, Simone
Statin-induced myopathic changes in primary human muscle cells and reversal by a prostaglandin F2 alpha analogue
title Statin-induced myopathic changes in primary human muscle cells and reversal by a prostaglandin F2 alpha analogue
title_full Statin-induced myopathic changes in primary human muscle cells and reversal by a prostaglandin F2 alpha analogue
title_fullStr Statin-induced myopathic changes in primary human muscle cells and reversal by a prostaglandin F2 alpha analogue
title_full_unstemmed Statin-induced myopathic changes in primary human muscle cells and reversal by a prostaglandin F2 alpha analogue
title_short Statin-induced myopathic changes in primary human muscle cells and reversal by a prostaglandin F2 alpha analogue
title_sort statin-induced myopathic changes in primary human muscle cells and reversal by a prostaglandin f2 alpha analogue
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005895/
https://www.ncbi.nlm.nih.gov/pubmed/32034223
http://dx.doi.org/10.1038/s41598-020-58668-2
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