This Article Full Text Full Text (PDF) All Versions of this Article: 103/5/e28    most recent CIRCRESAHA.108.181305v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ewence, A. E. Articles by Proudfoot, D. Search for Related Content PubMed PubMed Citation Articles by Ewence, A. E. Articles by Proudfoot, D.

(Circulation Research. 2008;103:e28.)
© 2008 American Heart Association, Inc.

Ultrarapid Communication

Calcium Phosphate Crystals Induce Cell Death in Human Vascular Smooth Muscle Cells

A Potential Mechanism in Atherosclerotic Plaque Destabilization

Alexandra E. Ewence, Martin Bootman, H. Llewelyn Roderick, Jeremy N. Skepper, Geraldine McCarthy, Matthias Epple, Markus Neumann, Catherine M. Shanahan, Diane Proudfoot

From the Division of Cardiovascular Medicine (A.E.E., D.P.), University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK; the Laboratory of Molecular Signalling (M.B., H.L.R.), The Babraham Institute, Babraham, Cambridge, UK; the Department of Anatomy (J.N.S.), Multi-Imaging Centre, University of Cambridge, Cambridge, UK; the Department of Clinical Pharmacology (G.M.), Royal College of Surgeons in Ireland, Dublin, UK; Inorganic Chemistry (M.E., M.N.), University of Duisburg-Essen, Essen, Germany; and Kings College London (C.M.S.), Cardiovascular Division, James Black Centre, London, UK; and the Department of Pharmacology (H.L.R.), University of Cambridge, UK.

Correspondence to Diane Proudfoot, Department of Medicine, University of Cambridge, ACCI Building, Level 6, Box 110, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 2QQ, UK. E-mail dianeproudfoot{at}gmail.com

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 µm 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.

Key Words: apoptosis • atherosclerosis • calcification • vascular smooth muscle cells

This article has been cited by other articles:

				H. Eddington and J. G. Heaf Clinical management of disturbances of calcium and phosphate metabolism in dialysis patients NDT Plus, August 1, 2009; 2(4): 267 - 272. [Abstract] [Full Text] [PDF]