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Analysis of the global RNA expression profiles of skeletal muscle cells treated with statins.
J Atheroscler Thromb. 2005; 12(3):121-31.JA

Abstract

The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are the most effective drugs for hypercholesteloremia. However, a significant side effect of statin treatment is rhabdomyolysis. In order to study the effect of statins in skeletal muscle cells, we used a DNA microarray analysis to investigate the changes in gene expression profiles brought about by statins in two skeletal muscle cell lines, namely, differentiated rat L6 myotubes and a human skeletal muscle cell line (hSkMC). In both cell lines, the statins (atorvastatin, cerivastatin and pitavastatin) induced the expression of four genes, which relate to cholesterol metabolism, namely, HMG-CoA synthase 1, HMG-CoA reductase, farnesyl diphosphate synthase and isopentenyl-diphosphate delta isomerase. Statin inhibited the synthesis of cholesterol at least five times more effectively in hSkMCs than in the hepatocytes. In addition, unlike in osteoblasts or coronary artery smooth muscle cells, statins upregulated the mRNA expression of cholesterol-associated enzymes in hSkMCs. These results provide basic information on skeletal muscle cells treated with statins and indicate that the cells are sensitive to the inhibition of HMG-CoA reductase, which may be related to the pathogenesis of muscle damage in statin therapy.

Authors+Show Affiliations

Laboratory for Systems Biology and Medicine, RCAST, The University of Tokyo, Tokyo, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16020911

Citation

Morikawa, Shigeru, et al. "Analysis of the Global RNA Expression Profiles of Skeletal Muscle Cells Treated With Statins." Journal of Atherosclerosis and Thrombosis, vol. 12, no. 3, 2005, pp. 121-31.
Morikawa S, Murakami T, Yamazaki H, et al. Analysis of the global RNA expression profiles of skeletal muscle cells treated with statins. J Atheroscler Thromb. 2005;12(3):121-31.
Morikawa, S., Murakami, T., Yamazaki, H., Izumi, A., Saito, Y., Hamakubo, T., & Kodama, T. (2005). Analysis of the global RNA expression profiles of skeletal muscle cells treated with statins. Journal of Atherosclerosis and Thrombosis, 12(3), 121-31.
Morikawa S, et al. Analysis of the Global RNA Expression Profiles of Skeletal Muscle Cells Treated With Statins. J Atheroscler Thromb. 2005;12(3):121-31. PubMed PMID: 16020911.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Analysis of the global RNA expression profiles of skeletal muscle cells treated with statins. AU - Morikawa,Shigeru, AU - Murakami,Takeshi, AU - Yamazaki,Hiroyuki, AU - Izumi,Akashi, AU - Saito,Yasushi, AU - Hamakubo,Takao, AU - Kodama,Tatsuhiko, PY - 2005/7/16/pubmed PY - 2005/10/21/medline PY - 2005/7/16/entrez SP - 121 EP - 31 JF - Journal of atherosclerosis and thrombosis JO - J Atheroscler Thromb VL - 12 IS - 3 N2 - The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are the most effective drugs for hypercholesteloremia. However, a significant side effect of statin treatment is rhabdomyolysis. In order to study the effect of statins in skeletal muscle cells, we used a DNA microarray analysis to investigate the changes in gene expression profiles brought about by statins in two skeletal muscle cell lines, namely, differentiated rat L6 myotubes and a human skeletal muscle cell line (hSkMC). In both cell lines, the statins (atorvastatin, cerivastatin and pitavastatin) induced the expression of four genes, which relate to cholesterol metabolism, namely, HMG-CoA synthase 1, HMG-CoA reductase, farnesyl diphosphate synthase and isopentenyl-diphosphate delta isomerase. Statin inhibited the synthesis of cholesterol at least five times more effectively in hSkMCs than in the hepatocytes. In addition, unlike in osteoblasts or coronary artery smooth muscle cells, statins upregulated the mRNA expression of cholesterol-associated enzymes in hSkMCs. These results provide basic information on skeletal muscle cells treated with statins and indicate that the cells are sensitive to the inhibition of HMG-CoA reductase, which may be related to the pathogenesis of muscle damage in statin therapy. SN - 1340-3478 UR - https://www.unboundmedicine.com/medline/citation/16020911/Analysis_of_the_global_RNA_expression_profiles_of_skeletal_muscle_cells_treated_with_statins_ L2 - http://joi.jlc.jst.go.jp/JST.JSTAGE/jat/12.121?from=PubMed DB - PRIME DP - Unbound Medicine ER -