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- Title
Effects of myosin heavy chain (MHC) plasticity induced by HMGCoA-reductase inhibition on skeletal muscle functions.
- Authors
Trapani, Laura; Melli, Luca; Segatto, Marco; Trezza, Viviana; Campolongo, Patrizia; Jozwiak, Adam; Swiezewska, Ewa; Pucillo, Leopoldo Paolo; Moreno, Sandra; Fanelli, Francesca; Linari, Marco; Pallottini, Valentina
- Abstract
The rate-limiting step of cholesterol biosynthetic pathway is catalyzed by 3-hydroxy-3-methylglutaryl coenzyme reductase (HGMR), whose inhibitors, the statins, widely used in clinical practice to treat hypercholesterolemia, often cause myopathy, and rarely rhabdomyolysis. All studies to date are limited to the definition of statin-induced myotoxicity omitting to investigate whether and how HMGR inhibition influences muscle functions. To this end, 3-mo-old male rats (Rattus norvegicus) were treated for 3 wk with a daily intraperitoneal injection of simvastatin (1.5 mg/kg/d), and biochemical, morphological, mechanical, and functional analysis were performed on extensor digitorum longus (EDL) muscle. Our results show that EDL muscles from simvastatin-treated rats exhibited reduced HMGR activity; a 15% shift from the fastest myosin heavy-chain (MHC) isoform lib to the slower Ila/x; and reduced power output and unloaded shortening velocity, by 41 and 23%, respectively, without any change in isometric force and endurance. Moreover, simvastatin-treated rats showed a decrease of maximum speed reached and the latency to fall off the rotaroad (~-30%). These results indicate that the molecular mechanism of the impaired muscle function following statin treatment could be related to die plasticity of fast MHC isoform expression.
- Subjects
CATALYSIS; CHOLESTEROL; REDUCTASES; STATINS (Cardiovascular agents); PHARMACODYNAMICS; MUSCLES; MYOSIN
- Publication
FASEB Journal, 2011, Vol 25, Issue 11, p4037
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.11-184218