Journal of Atherosclerosis and Thrombosis
Online ISSN : 1880-3873
Print ISSN : 1340-3478
Original Articles
Statin-Induced Ca2+ Release was Increased in B Lymphocytes in Patients who Showed Elevated Serum Creatine Kinase During Statin Treatment
Takayuki HattoriKuniaki SaitoMasao TakemuraHiroyasu ItoHirotoshi OhtaHisayasu WadaYoshitatsu SeiMitsunobu KawamuraMitsuru Seishima
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Volume 16 (2009) Issue 6 Pages 870-877

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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 intracellular 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 contribute 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.

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