Long‐term atorvastatin treatment inhibited pro‐survival signaling, reduced mitochondrial function and altered ultrastructural integrity in cardiac myocytes (1095.6)
| Autor: | Elizabeth Asfaw, Joseph C. Godoy, Ingrid R. Niesman, Jan M. Schilling, Alice E. Zemljic-Harpf, Hemal H. Patel, Erika A. Alvarez, Nancy Dalton, Anna Schwarz, Adam Kassan |
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| Rok vydání: | 2014 |
| Předmět: |
Statin
business.industry medicine.drug_class Atorvastatin Cardiac muscle nutritional and metabolic diseases Skeletal muscle Pharmacology Biochemistry medicine.anatomical_structure Genetics medicine Myocyte lipids (amino acids peptides and proteins) cardiovascular diseases medicine.symptom business Myopathy Molecular Biology Protein kinase B Pravastatin Biotechnology medicine.drug |
| Zdroj: | The FASEB Journal. 28 |
| ISSN: | 1530-6860 0892-6638 |
| DOI: | 10.1096/fasebj.28.1_supplement.1095.6 |
| Popis: | Introduction: Statins are widely used to lower low-density lipoprotein cholesterol (LDL-C) for prevention of cardiovascular disease. The FDA warns that statins may induce skeletal muscle side effects. Skeletal muscle biopsies from patients with statin myopathy showed defects in mitochondrial ultrastructure. Impaired mitochondrial function was postulated as a key cause of statin-induced myopathy. Long-term statin effects on cardiac muscle are currently unclear. Methods and Results: Neonatal cardiac myocytes were treated with either atorvastatin (lipophilic) or pravastatin (hydrophilic) for up to 48 hours (both at 1-10 μM). Atorvastatin, but not pravastatin, inhibited RhoA activation, reduced mTOR/AKT signaling, and induced apoptosis. Further, atorvastatin treatment reduced protein expression of caveolin, dystrophin and epidermal growth factor receptor in cardiac myocytes. Both statins induced ER stress responses, but only atorvastatin increased CHOP initiated apoptotic cell death. Assessment of mitochondri... |
| Databáze: | OpenAIRE |
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