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Abstract Title:

Statin-induced Ca(2+) release was increased in B lymphocytes in patients who showed elevated serum creatine kinase during statin treatment.

Abstract Source:

J Atheroscler Thromb. 2009;16(6):870-7. Epub 2009 Dec 22. PMID: 20032581

Abstract Author(s):

Takayuki Hattori, Kuniaki Saito, Masao Takemura, Hiroyasu Ito, Hirotoshi Ohta, Hisayasu Wada, Yoshitatsu Sei, Mitsunobu Kawamura, Mitsuru Seishima

Article Affiliation:

Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, Japan.

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 Ca(2+) homeostasis in muscle cells, we tested whether measuring statin-induced changes in intracellular calcium ([Ca(2+)](i)) is useful for predicting susceptibility to statin-muscle damage, using human CD19+ primary B lymphocytes. METHODS: Statin-induced alterations in [Ca(2+)](i) were studied using the human THP-1 cell line and CD19+ primary B lymphocytes. Changes in [Ca(2+)](i) were measured directly in fluo-3- loaded cells using either single or dual-color flow cytometry. RESULTS: The Ca(2+) release study suggested that statin-induced changes in [Ca(2+)](i) were due to Ca(2+) release from ryanodine-sensitive Ca(2+) stores and mitochondrial compartments. Further, statin users who experienced elevated creatine kinase (n=8) exhibited significantly greater statin-induced Ca(2+) 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 Ca(2+) release from ryanodine-sensitive stores and mitochondria may contribute to myotoxicity. The laboratory test for Ca(2+) release using CD19+ primary B lymphocytes may be useful to predict susceptibility to statin-induced muscle toxicity prior to statin use.

Study Type : In Vitro Study
Additional Links
Adverse Pharmacological Actions : Myotoxicity : CK(327) : AC(80)

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Sayer Ji
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