Statin-Induced Ca²⁺ Release was Increased in B Lymphocytes in Patients who Showed Elevated Serum Creatine Kinase During Statin Treatment

Abstract

Aim: Statins are effective in lowering cholesterol levels, but cause fatal rhabdomyolysis in susceptible individuals. Because it has been hypothesized that muscle damage could result from alterations in Ca²⁺ homeostasis in muscle cells, we tested whether measuring statin-induced changes in intracellu-lar calcium ([Ca²⁺]_i) is useful for predicting susceptibility to statin-muscle damage, using human CD19+ primary B lymphocytes.
Methods: Statin-induced alterations in [Ca²⁺]_i were studied using the human THP-1 cell line and CD19+ primary B lymphocytes. Changes in [Ca²⁺]_i were measured directly in fluo-3- loaded cells using either single or dual-color flow cytometry.
Results: The Ca²⁺ release study suggested that statin-induced changes in [Ca²⁺]_i were due to Ca²⁺ release from ryanodine-sensitive Ca²⁺ stores and mitochondrial compartments. Further, statin users who experienced elevated creatine kinase (n=8) exhibited significantly greater statin-induced Ca²⁺ release in B cells than healthy volunteers (n=45) and statin users without elevated creatine kinase (n=16), while no difference was seen between the latter two groups.
Conclusion: Statin-induced Ca²⁺ release from ryanodine-sensitive stores and mitochondria may con-tribute to myotoxicity. The laboratory test for Ca²⁺ release using CD19+ primary B lymphocytes may be useful to predict susceptibility to statin-induced muscle toxicity prior to statin use.