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Calcium phosphate crystals induce cell death in human vascular smooth muscle cells: a potential mechanism in atherosclerotic plaque destabilization

Ewence, Alexandra E.; Bootman, Martin D.; Roderick, H. Llewelyn; Skepper, Jeremy N.; McCarthy, Geraldine; Epple, Matthias; Neumann, Markus; Shanahan, Catherine M. and Proudfoot, Diane (2008). Calcium phosphate crystals induce cell death in human vascular smooth muscle cells: a potential mechanism in atherosclerotic plaque destabilization. Circulation Research, 103(5) e28-e34.

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DOI (Digital Object Identifier) Link:​CIRCRESAHA.108.181305
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Vascular calcification is associated with an increased risk of myocardial infarction; however, the mechanisms linking these 2 processes are unknown. Studies in macrophages have suggested that calcium phosphate crystals induce the release of proinflammatory cytokines; however, no studies have been performed on the effects of calcium phosphate crystals on vascular smooth muscle cell function. In the present study, we found that calcium phosphate crystals induced cell death in human aortic vascular smooth muscle cells with their potency depending on their size and composition. Calcium phosphate crystals of approximately 1 microm or less in diameter caused rapid rises in intracellular calcium concentration, an effect that was inhibited by the lysosomal proton pump inhibitor, bafilomycin A1. Bafilomycin A1 also blocked vascular smooth muscle cell death suggesting that crystal dissolution in lysosomes leads to an increase in intracellular calcium levels and subsequent cell death. These studies give novel insights into the bioactivity of calcified deposits and suggest that small calcium phosphate crystals could destabilize atherosclerotic plaques by initiating inflammation and by causing vascular smooth muscle cell death.

Item Type: Journal Item
Copyright Holders: 2008 American Heart Association, Inc.
ISSN: 1524-4571
Keywords: apoptosis; atherosclerosis; calcification; vascular smooth muscle cells
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
Interdisciplinary Research Centre: Biomedical Research Network (BRN)
Health and Wellbeing PRA (Priority Research Area)
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Item ID: 34867
Depositing User: Martin Bootman
Date Deposited: 24 Oct 2012 13:17
Last Modified: 11 Sep 2017 15:32
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