Statin therapy and the expression of genes that regulate calcium homeostasis and membrane repair in skeletal muscle

Draeger, Annette; Sanchez-Freire, Verónica; Monastyrskaya, Katia; Hoppeler, Hans; Mueller, Matthias; Breil, Fabio; Mohaupt, Markus G; Babiychuk, Eduard B (2010). Statin therapy and the expression of genes that regulate calcium homeostasis and membrane repair in skeletal muscle. American journal of pathology, 177(1), pp. 291-9. New York, N.Y.: Elsevier 10.2353/ajpath.2010.091140

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In skeletal muscle of patients with clinically diagnosed statin-associated myopathy, discrete signs of structural damage predominantly localize to the T-tubular region and are suggestive of a calcium leak. The impact of statins on skeletal muscle of non-myopathic patients is not known. We analyzed the expression of selected genes implicated in the molecular regulation of calcium and membrane repair, in lipid homeostasis, myocyte remodeling and mitochondrial function. Microscopic and gene expression analyses were performed using validated TaqMan custom arrays on skeletal muscle biopsies of 72 age-matched subjects who were receiving statin therapy (n = 38), who had discontinued therapy due to statin-associated myopathy (n = 14), and who had never undergone statin treatment (n = 20). In skeletal muscle, obtained from statin-treated, non-myopathic patients, statins caused extensive changes in the expression of genes of the calcium regulatory and the membrane repair machinery, whereas the expression of genes responsible for mitochondrial function or myocyte remodeling was unaffected. Discontinuation of treatment due to myopathic symptoms led to a normalization of gene expression levels, the genes encoding the ryanodine receptor 3, calpain 3, and dystrophin being the most notable exceptions. Hence, even in clinically asymptomatic (non-myopathic) patients, statin therapy leads to an upregulation in the expression of genes that are concerned with skeletal muscle regulation and membrane repair.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Cell Biology
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension

UniBE Contributor:

Draeger, Annette; Sanchez Freire, Veronica; Monastyrskaya-Stäuber, Katia; Hoppeler, Hans-Heinrich; Breil, Fabio; Mohaupt, Markus and Babiychuk, Eduard

ISSN:

0002-9440

Publisher:

Elsevier

Language:

English

Submitter:

Markus Georg Mohaupt

Date Deposited:

04 Oct 2013 14:09

Last Modified:

26 Feb 2014 04:37

Publisher DOI:

10.2353/ajpath.2010.091140

PubMed ID:

20489141

Web of Science ID:

000279805100031

URI:

https://boris.unibe.ch/id/eprint/936 (FactScience: 201533)

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