title: Annexin A1 is a biomarker of T-tubular repair in skeletal muscle of nonmyopathic patients undergoing statin therapy.
abstract: Skeletal muscle complaints are a common consequence of cholesterol-lowering therapy. Transverse tubular (T-tubular) vacuolations occur in patients having statin-associated myopathy and, to a lesser extent, in statin-treated patients without myopathy. We have investigated quantitative changes in T-tubular morphology and looked for early indicators of T-tubular membrane repair in skeletal muscle biopsy samples from patients receiving cholesterol-lowering therapy who do not have myopathic side effects. Gene expression and protein levels of incipient membrane repair proteins were monitored in patients who tolerated statin treatment without myopathy and in statin-naive subjects. In addition, morphometry of the T-tubular system was performed. Only the gene expression for annexin A1 was up-regulated, whereas the expression of other repair genes remained unchanged. However, annexin A1 and dysferlin protein levels were significantly increased. In statin-treated patients, the volume fraction of the T-tubular system was significantly increased, but the volume fraction of the sarcoplasmic reticulum remained unchanged. A complex surface structure in combination with high mechanical loads makes skeletal muscle plasma membranes susceptible to injury. Ca(2+)-dependent membrane repair proteins such as dysferlin and annexin A1 are deployed at T-tubular sites. The up-regulation of annexin A1 gene expression and protein points to this protein as a biomarker for T-tubular repair.
authors: Institute of Anatomy, Inselspital, University of Bern, Bern, Switzerland.
authors: Tilman
authors: T
authors: Voigt
authors: Hans-Jörg
authors: HJ
authors: Sebald
authors: Roman
authors: R
authors: Schoenauer
authors: Soledad
authors: S
authors: Levano
authors: Thierry
authors: T
authors: Girard
authors: Hans H
authors: HH
authors: Hoppeler
authors: Eduard B
authors: EB
authors: Babiychuk
authors: Annette
authors: A
authors: Draeger
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017305:Annexin A1 / Q000096:biosynthesis* / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000293:injuries / Q000503:physiopathology*; D012038:Regeneration / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D017305:Annexin A1; D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
keywords: Ca2+-dependent translocation; dysferlin; plasma membrane repair