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

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

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)870-877
Number of pages8
JournalJournal of atherosclerosis and thrombosis
Volume16
Issue number6
DOIs
Publication statusPublished - 2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine
  • Biochemistry, medical

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