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Statin-Induced Ca2+ Release was Increased in B Lymphocytes in Patients who Showed Elevated Serum Creatine Kinase During Statin Treatment
- Source :
- Journal of Atherosclerosis and Thrombosis. 16:870-877
- Publication Year :
- 2009
- Publisher :
- Japan Atherosclerosis Society, 2009.
-
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.
- Subjects :
- medicine.medical_specialty
Statin
biology
Ryanodine receptor
medicine.drug_class
Biochemistry (medical)
nutritional and metabolic diseases
Pharmacology
medicine.disease
Calcium in biology
Endocrinology
Internal medicine
Toxicity
Internal Medicine
medicine
biology.protein
Myocyte
lipids (amino acids, peptides, and proteins)
Creatine kinase
cardiovascular diseases
Cardiology and Cardiovascular Medicine
Rhabdomyolysis
Homeostasis
Subjects
Details
- ISSN :
- 18803873 and 13403478
- Volume :
- 16
- Database :
- OpenAIRE
- Journal :
- Journal of Atherosclerosis and Thrombosis
- Accession number :
- edsair.doi...........9f2ba83efd6bd9eaa609369c93c8e023