Genesis and growth of extracellular-vesicle-derived microcalcification in atherosclerotic plaques

Clinical evidence links arterial calcification and cardiovascular risk. Finite-element modelling of the stress distribution within atherosclerotic plaques has suggested that subcellular microcalcifications in the fibrous cap may promote material failure of the plaque, but that large calcifications c...

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Bibliographic Details
Published in:Nature materials Vol. 15; no. 3; pp. 335 - 343
Main Authors: Hutcheson, Joshua D., Goettsch, Claudia, Bertazzo, Sergio, Maldonado, Natalia, Ruiz, Jessica L., Goh, Wilson, Yabusaki, Katsumi, Faits, Tyler, Bouten, Carlijn, Franck, Gregory, Quillard, Thibaut, Libby, Peter, Aikawa, Masanori, Weinbaum, Sheldon, Aikawa, Elena
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 01.03.2016
Nature Publishing Group
Subjects:
140/146
639/166
639/301/54
Animals
Apolipoproteins E - genetics
Apolipoproteins E - metabolism
Atherosclerosis
Atherosclerosis - metabolism
Biomaterials
Calcification
Calcium - metabolism
Carotid Arteries - pathology
Collagen
Collagen - metabolism
Collagens
Condensed Matter Physics
Coronary Disease - metabolism
Extracellular Matrix
Extracellular Vesicles - physiology
Failure
Formations
Genesis
Health risks
Humans
Hydrogels
Materials Science
Mice
Mice, Knockout
Minerals
Nanotechnology
Optical and Electronic Materials
Stress analysis
Three dimensional
ISSN:1476-1122, 1476-4660, 1476-4660
Online Access:Get full text
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Summary:Clinical evidence links arterial calcification and cardiovascular risk. Finite-element modelling of the stress distribution within atherosclerotic plaques has suggested that subcellular microcalcifications in the fibrous cap may promote material failure of the plaque, but that large calcifications can stabilize it. Yet the physicochemical mechanisms underlying such mineral formation and growth in atheromata remain unknown. Here, by using three-dimensional collagen hydrogels that mimic structural features of the atherosclerotic fibrous cap, and high-resolution microscopic and spectroscopic analyses of both the hydrogels and of calcified human plaques, we demonstrate that calcific mineral formation and maturation results from a series of events involving the aggregation of calcifying extracellular vesicles, and the formation of microcalcifications and ultimately large calcification areas. We also show that calcification morphology and the plaque’s collagen content—two determinants of atherosclerotic plaque stability—are interlinked. The formation of atherosclerotic plaques involves the aggregation of calcifying extracellular vesicles and the formation of microcalcifications.
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ISSN:1476-1122
1476-4660
1476-4660
DOI:10.1038/nmat4519