Impact of Atorvastatin on Skeletal Muscle Mitochondrial Activity,Locomotion and Axonal Excitability—Evidence from ApoE-/- Mice |
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Authors: | Chiara Macchi Veronica Bonalume Maria Francesca Greco Marta Mozzo Valentina Melfi Cesare R Sirtori Valerio Magnaghi Alberto Corsini Massimiliano Ruscica |
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Affiliation: | Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, 20133 Milan, Italy; (C.M.); (V.B.); (M.F.G.); (M.M.); (V.M.); (C.R.S.); (V.M.); (A.C.) |
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Abstract: | The cardiovascular benefit of statins is well established. However, only 20% of high-risk patients remain adequately adherent after 5 years of treatment. Among reasons for discontinuation, statin associated-muscle pain symptoms are the most prevalent. Aim of the present study was to evaluate the impact of high dose atorvastatin on skeletal muscle mitochondrial activity, aerobic and anaerobic exercise, and axonal excitability in a murine model of atherosclerosis. ApoE-/- mice were fed 12 weeks a high-fat high-cholesterol diet alone or containing atorvastatin (40 mg/Kg/day). Outcomes were the evaluation of muscle mitochondrial functionality, locomotion, grip test, and axonal excitability (compound action potential recording analysis of Aα motor propioceptive, Aβ mechanoceptive and C nociceptive fibres). Atorvastatin led to a reduction in muscle mitochondrial biogenesis and mitochondrial ATP production. It did not affect muscular strength but led to a time-dependent motor impairment. Atorvastatin altered the responsiveness of mechanoceptive and nociceptive fibres, respectively, the Aβ and C fibres. These findings point out to a mild sensitization on mechanical, tactile and pain sensitivity. In conclusion, although the prevalence of muscular side effects from statins may be overestimated, understanding of the underlying mechanisms can help improve the therapeutic approach and reassure adherence in patients needing-to-be-treated. |
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Keywords: | statins atorvastatin mitochondria locomotion muscles grip test |
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