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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:2030.)
© 2008 American Heart Association, Inc.

Cell Biology/Signaling

Mineral Surface in Calcified Plaque Is Like That of Bone

Further Evidence for Regulated Mineralization

Melinda J. Duer; Tomislav Frii; Diane Proudfoot; David G. Reid; Michael Schoppet; Catherine M. Shanahan; Jeremy N. Skepper; Erica R. Wise

From the Departments of Chemistry (M.J.D., T.F., D.G.R., E.R.W.), Medicine (D.P.), and Physiology, Development, & Neuroscience (J.N.S.), University of Cambridge, UK; the Department of Internal Medicine and Cardiology (M.S.), Philipps-University, Marburg, Germany; and the Cardiovascular Division (C.M.S.), Kings College London, UK.

Correspondence to Melinda J. Duer, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK. E-mail mjd13{at}cam.ac.uk

Objectives— Cell biological studies demonstrate remarkable similarities between mineralization processes in bone and vasculature, but knowledge of the components acting to initiate mineralization in atherosclerosis is limited. The molecular level microenvironment at the organic-inorganic interface holds a record of the mechanisms controlling mineral nucleation. This study was undertaken to compare the poorly understood interface in mineralized plaque with that of bone, which is considerably better characterized.

Methods and Results— Solid state nuclear magnetic resonance (SSNMR) spectroscopy provides powerful tools for studying the organic-inorganic interface in calcium phosphate biominerals. The rotational echo double resonance (REDOR) technique, applied to calcified human plaque, shows that this interface predominantly comprises sugars, most likely glycosaminoglycans (GAGs). In this respect, and in the pattern of secondary effects seen to protein (mainly collagen), calcified plaque strongly resembles bone.

Conclusion— The similarity between biomineral formed under highly controlled (bone) and pathological (plaque) conditions suggests that the control mechanisms are more similar than previously thought, and may be adaptive. It is strong further evidence for regulation of plaque mineralization by osteo/chondrocytic vascular smooth muscle cells.

NMR techniques show that bone and vascular calcifications are very similar with respect to constituents of the mineral/matrix interface, a predominant component being glycosaminoglycans. This implies that regulation of both is very similar, supporting cell biological studies showing pathological calcification of vascular smooth muscle cells to be a regulated process.

Key Words: atherosclerosis • biomineralization • glycosaminoglycans • nuclear magnetic resonance spectroscopy • vascular calcification

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