Pathophysiological mechanisms of statin‐associated myopathies: possible role of the ubiquitin‐proteasome system

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...

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Main Authors: Amirhossein Sahebkar (Author), Arrigo F.G. Cicero (Author), Paolo Di Giosia (Author), Irene Pomilio (Author), Cosimo Andrea Stamerra (Author), Paolo Giorgini (Author), Claudio Ferri (Author), Stephan vonHaehling (Author), Maciej Banach (Author), Tannaz Jamialahmadi (Author)
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Published: Wiley, 2020-10-01T00:00:00Z.
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001 doaj_20570d2b6cdd4ed6a8446b96d1e08dba
042 |a dc 
100 1 0 |a Amirhossein Sahebkar  |e author 
700 1 0 |a Arrigo F.G. Cicero  |e author 
700 1 0 |a Paolo Di Giosia  |e author 
700 1 0 |a Irene Pomilio  |e author 
700 1 0 |a Cosimo Andrea Stamerra  |e author 
700 1 0 |a Paolo Giorgini  |e author 
700 1 0 |a Claudio Ferri  |e author 
700 1 0 |a Stephan vonHaehling  |e author 
700 1 0 |a Maciej Banach  |e author 
700 1 0 |a Tannaz Jamialahmadi  |e author 
245 0 0 |a Pathophysiological mechanisms of statin‐associated myopathies: possible role of the ubiquitin‐proteasome system 
260 |b Wiley,   |c 2020-10-01T00:00:00Z. 
500 |a 2190-6009 
500 |a 2190-5991 
500 |a 10.1002/jcsm.12579 
520 |a 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. 
546 |a EN 
690 |a Statins 
690 |a Myopathy 
690 |a Ubiquitin‐proteasome system 
690 |a Diseases of the musculoskeletal system 
690 |a RC925-935 
690 |a Human anatomy 
690 |a QM1-695 
655 7 |a article  |2 local 
786 0 |n Journal of Cachexia, Sarcopenia and Muscle, Vol 11, Iss 5, Pp 1177-1186 (2020) 
787 0 |n https://doi.org/10.1002/jcsm.12579 
787 0 |n https://doaj.org/toc/2190-5991 
787 0 |n https://doaj.org/toc/2190-6009 
856 4 1 |u https://doaj.org/article/20570d2b6cdd4ed6a8446b96d1e08dba  |z Connect to this object online.