Effect of statins on the viability of macrophages and smooth muscle cells
| Autor: | Inge De Meyer, Sander M. Houten, Guido R.Y. De Meyer, Hidde Bult, Wim Martinet, Arnold G. Herman, Valerie Croons |
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| Přispěvatelé: | Paediatric Metabolic Diseases, Laboratory Genetic Metabolic Diseases |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Male
Programmed cell death Cell Survival Myocytes Smooth Muscle Apoptosis Biology Pharmacology Cell Line Mice medicine polycyclic compounds Macrophage Animals Aorta Mice Inbred BALB C Macrophages Pharmacology. Therapy nutritional and metabolic diseases Mice Inbred C57BL Simvastatin Immunology Macrophages Peritoneal Female Hydroxymethylglutaryl CoA Reductases lipids (amino acids peptides and proteins) Mevalonate pathway Lovastatin Rabbits Hydroxymethylglutaryl-CoA Reductase Inhibitors Cardiology and Cardiovascular Medicine Pravastatin Fluvastatin medicine.drug |
| Zdroj: | Journal of cardiovascular pharmacology Journal of cardiovascular pharmacology, 55(3), 269-275. Lippincott Williams and Wilkins |
| ISSN: | 0160-2446 |
| Popis: | Because macrophages play an important role in the destabilization of atherosclerotic plaques, and smooth muscle cells (SMCs) contribute to plaque stability, selective clearance of macrophages in atherosclerotic plaques is a promising strategy for plaque stabilization. In the present study, we investigated the effects of fluvastatin, simvastatin, lovastatin, and pravastatin on the viability of macrophages and SMCs. All statins, except pravastatin, induced cell death of J774A.1 macrophages after 24 hours, albeit with different sensitivity. The viability of rabbit aortic SMCs was hardly affected. Fluvastatin-induced macrophage cell death was characterized as apoptosis and could be reversed by isoprenoid intermediates of the mevalonate pathway. Peritoneal macrophages from male or female mice were much more resistant to statin-induced cell death. The high sensitivity of J774A.1 macrophages to statin-induced cell death was related to the strong 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in these cells. Macrophage and SMC content of rabbit atherosclerotic plaques was not affected after in vitro treatment with fluvastatin or lovastatin for 3 days. In conclusion, fluvastatin, simvastatin, and lovastatin, but not pravastatin, can selectively induce apoptosis in J774A.1 macrophages, but not in SMCs, primary macrophages or rabbit atherosclerotic plaques. This effect was related to the degree of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in the different cell types. |
| Databáze: | OpenAIRE |
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