Survey of muscle characteristics after statin-induced rhabdomyolysis

Aims: The etiology of statin-induced rhabdomyolysis (SIR) remains obscure. Most explanations claim deficiency of one of the main end products of the HMG-CoA reductase pathway. Experimental work has rarely tested the skeletal muscle of humans after SIR. Methods: We compared muscle from ten SIR patients with muscle from eight age-matched, statin-naive control subjects. We evaluated differences in muscle histochemistry, sterol biochemistry, prenylated proteins, atrogin-1 and mitochondrial content to assess which characteristics distinguished the rhabdomyolysis reaction from normal age-matched muscle. Results: Plant sterols were significantly increased in muscle from SIR subjects compared with ontrol subjects. Ras was significantly reduced and there was a trend towards increased atrogin-1 in SIR subjects compared with ontrol subject muscle. There was no difference in cholesterol concentrations, mitochondrial content or coenzyme Q₁₀ between groups. Conclusions: This evaluation of muscle from a small sample of patients with SIR demonstrates that differences in sitosterol:cholesterol ratio, the prenylated protein Ras and signals for muscle atrophy like atrogin-1, may distinguish this reaction from normal muscle.