
Pathophysiological mechanisms of statin‐associated myopathies: possible role of the ubiquitin‐proteasome system
Author(s) -
Sahebkar Amirhossein,
Cicero Arrigo F.G.,
Di Giosia Paolo,
Pomilio Irene,
Stamerra Cosimo Andrea,
Giorgini Paolo,
Ferri Claudio,
Haehling Stephan,
Banach Maciej,
Jamialahmadi Tannaz
Publication year - 2020
Publication title -
journal of cachexia, sarcopenia and muscle
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.803
H-Index - 66
eISSN - 2190-6009
pISSN - 2190-5991
DOI - 10.1002/jcsm.12579
Subject(s) - myopathy , proteasome , ubiquitin , myalgia , medicine , statin , protein degradation , muscle weakness , myocyte , bioinformatics , pharmacology , biology , microbiology and biotechnology , biochemistry , gene
Background Statins are the cornerstone of pharmacotherapy for atherosclerotic cardiovascular disease. While these drugs are generally safe, treatment adherence is not optimal in a considerable proportion of patients because of the adverse effects on skeletal muscles in the forms of myopathy, myalgia, muscular pain, nocturnal muscle cramping, weakness, and rare rhabdomyolysis. Methods For the purpose of this narrative review, we searched for the literature suggesting the involvement of the ubiquitin–proteasome system in the development of statin–induced myopathy. Results Statins have been shown to up–regulate the expression of the muscle–specific ubiquitin–proteasome system as the major non–lysosomal intracellular protein degradation system. It has been postulated that statins may provoke instability in the myocyte cell membrane when subjected to eccentric exercise stress, triggering activation of intracellular proteolytic cascades and changes in protein degradation machinery. This is accompanied by the up–regulation of a series of genes implicated in protein catabolism, in addition to those of the ubiquitin–proteasome system. Conclusions Based on the available literature, it seems that the involvement of ubiquitin–proteasome system is potentially implicated in the pathophysiology of statin–induced myopathy.