Effects of myosin heavy chain (MHC) plasticity induced by HMGCoA-reductase inhibition on skeletal muscle functions

Article

关键词: COENZYME-A REDUCTASE;    SHORTENING VELOCITY;    PLASMA-CHOLESTEROL;    STATIN THERAPY;    COA REDUCTASE;    OLDER-ADULTS;    BODY-SIZE;    RAT;    SIMVASTATIN;    FIBERS;   

DOI  :  10.1096/fj.11-184218

来源: SCIE

【 摘 要 】

The rate-limiting step of cholesterol bio-synthetic 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 IIb to the slower IIa/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 (similar to = 30%). These results indicate that the molecular mechanism of the impaired muscle function following statin treatment could be related to the plasticity of fast MHC isoform expression.-Trapani, L., Melli, L., Segatto, M., Trezza, V., Campolongo, P., Jozwiak, A., Swiezewska, E., Pucillo, L. P., Moreno, S., Fanelli, F., Linari, M., Pallottini, V. Effects of myosin heavy chain (MHC) plasticity induced by HMGCoA-reductase inhibition on skeletal muscle functions. FASEB J. 25, 4037-4047 (2011). www.fasebj.org

【 授权许可】

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