Paradoxical Effects of Statins on Aortic Valve Myofibroblasts and Osteoblasts
- 1 March 2005
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Arteriosclerosis, Thrombosis, and Vascular Biology
- Vol. 25 (3), 592-597
- https://doi.org/10.1161/01.atv.0000154278.01871.64
Abstract
Objectives— We evaluated the effects of statins on aortic valve myofibroblasts (AVMFs) and osteoblast calcification in vitro. Methods and Results— Cultured porcine AVMFs and M2–10B4 cells were treated with simvastatin and pravastatin. Mevalonate, a 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase metabolite, was added in parallel experiments. Manumycin A, which inhibits protein prenylation, was added to cultures in the absence of statins. Calcification was assessed by counting the number of calcific nodules formed and measuring alkaline phosphatase activity (APA). Statins inhibited calcific nodule formation ( P P P P P P Conclusions— Statins inhibit calcification in AVMFs by inhibiting the cholesterol biosynthetic pathway, independent of protein prenylation, but paradoxically stimulate bone cell calcification. Because 15% of patients with end-stage valvular heart disease exhibit mature bone in their aortic valves, statins may differentially regulate calcification within a valve, limiting dystrophic calcification but promoting ossification of formed bone.Keywords
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