Annexin A1 is a biomarker of T-tubular repair in skeletal muscle of nonmyopathic patients undergoing statin therapy

Voigt, Tilman; Sebald, Hans-Jörg; Schoenauer, Roman; Levano, Soledad; Girard, Thierry; Hoppeler, Hans H.; Babiychuk, Eduard B.; Draeger, Annette (2013). Annexin A1 is a biomarker of T-tubular repair in skeletal muscle of nonmyopathic patients undergoing statin therapy. FASEB journal, 27(6), pp. 2156-2164. Federation of American Societies for Experimental Biology 10.1096/fj.12-219345

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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.

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

UniBE Contributor:

Voigt, Tilman; Schönauer, Roman; Hoppeler, Hans-Heinrich; Babiychuk, Eduard and Draeger, Annette

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0892-6638

Publisher:

Federation of American Societies for Experimental Biology

Language:

English

Submitter:

Dierk Matthäus

Date Deposited:

13 Feb 2014 16:18

Last Modified:

13 Sep 2017 13:50

Publisher DOI:

10.1096/fj.12-219345

PubMed ID:

23413360

Uncontrolled Keywords:

Ca2+-dependent translocation dysferlin plasma membrane repair

BORIS DOI:

10.7892/boris.41535

URI:

https://boris.unibe.ch/id/eprint/41535

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