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

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Item Type:Article
Title:Statin-induced myopathic changes in primary human muscle cells and reversal by a prostaglandin F2 alpha analogue
Creators Name:Grunwald, S.A. and Popp, O. and Haafke, S. and Jedraszczak, N. and Grieben, U. and Saar, K. and Patone, G. and Kress, W. and Steinhagen-Thiessen, E. and Dittmar, G. and Spuler, S.
Abstract: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.
Keywords:Anticholesteremic Agents, Cell Differentiation, Cell Proliferation, Cultured Cells, Dinoprost, Rosuvastatin Calcium, Simvastatin, Skeletal Muscle Fibers, Transcriptome
Source:Scientific Reports
Publisher:Nature Publishing Group
Page Range:2158
Date:7 February 2020
Official Publication:https://doi.org/10.1038/s41598-020-58668-2
PubMed:View item in PubMed

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