Statins inhibit in vitro calcification of human vascular smooth muscle cells induced by inflammatory mediators
| Autor: | Shuichi Jono, Akane Kizu, Yoshiki Nishizawa, Yasuhisa Okuno, Hidenori Koyama, Atsushi Shioi |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
medicine.medical_specialty
Vascular smooth muscle RHOA Pyridines Atorvastatin Myocytes Smooth Muscle Mevalonic Acid Inflammation Pharmacology Biochemistry Muscle Smooth Vascular Polyisoprenyl Phosphates Internal medicine medicine Humans Pyrroles Molecular Biology Rho-associated protein kinase Dose-Response Relationship Drug biology Calcinosis Cerivastatin Cell Biology Alkaline Phosphatase medicine.disease Endocrinology Heptanoic Acids biology.protein Hydroxymethylglutaryl-CoA Reductase Inhibitors medicine.symptom Aortic valve calcification Sesquiterpenes Calcification medicine.drug |
| Zdroj: | Journal of Cellular Biochemistry. 93:1011-1019 |
| ISSN: | 1097-4644 0730-2312 |
| DOI: | 10.1002/jcb.20207 |
| Popis: | Although lipid-lowering therapy with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) decreases the progression of coronary artery and aortic valve calcification, the mechanism of action of these drugs to inhibit the calcification process remains unclear. In this study, we investigated the effect of statins such as cerivastatin and atorvastatin on vascular calcification by utilizing an in vitro model of inflammatory vascular calcification. Cerivastatin and atorvastatin dose-dependently inhibited in vitro calcification of human vascular smooth muscle cells (HVSMCs) induced by the following inflammatory mediators (IM): interferon-gamma, 1alpha,25-dihydroxyvitamin D3, tumor necrosis factor-alpha, and oncostatin M. These statins also depressed expression of alkaline phosphatase (ALP) in HVSMCs induced by these factors. Mevalonate and geranylgeranylpyrophosphate reversed the inhibitory effect of cerivastatin on ALP expression in HVSMCs, while farnesylpyrophosphate showed no effect on the ALP activities inhibited by this drug, suggesting that inhibition of Rho and its downstream target, Rho kinase may mediate the inhibitory effect of cerivastatin. Cerivastatin prevented RhoA activation in HVSMCs induced by the IM. A specific inhibitor of Rho kinase (Y-27632) inhibited in vitro calcification and induction of ALP in HVSMCs. These findings provide a possible mechanism of statins to prevent the progression of calcification in inflammatory vascular diseases such as atherosclerosis and cardiac valvular calcification. |
| Databáze: | OpenAIRE |
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