title: Statin therapy and the expression of genes that regulate calcium homeostasis and membrane repair in skeletal muscle.
abstract: 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.
authors.affiliation: Institute of Anatomy, University of Bern, Baltzerstr. 2, 3012 Bern, Switzerland. draeger@ana.unibe.ch
authors.forename: Annette
authors.initials: A
authors.lastname: Draeger
authors.forename: Verónica
authors.initials: V
authors.lastname: Sanchez-Freire
authors.forename: Katia
authors.initials: K
authors.lastname: Monastyrskaya
authors.forename: Hans
authors.initials: H
authors.lastname: Hoppeler
authors.forename: Matthias
authors.initials: M
authors.lastname: Mueller
authors.forename: Fabio
authors.initials: F
authors.lastname: Breil
authors.forename: Markus G
authors.initials: MG
authors.lastname: Mohaupt
authors.forename: Eduard B
authors.initials: EB
authors.lastname: Babiychuk
mesh_terms: D000368:Aged; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006706:Homeostasis / Q000235:genetics*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000494:pharmacology; D006937:Hypercholesterolemia / Q000188:drug therapy; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D009135:Muscular Diseases / Q000139:chemically induced / Q000235:genetics / Q000473:pathology
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002118:Calcium