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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Vydané v:	Nature materials Ročník 15; číslo 3; s. 335 - 343
Hlavní autori:	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
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	London Nature Publishing Group UK 01.03.2016 Nature Publishing Group
Predmet:	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
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Shrnutí:	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.
Bibliografia:	SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 14 ObjectType-Article-1 ObjectType-Feature-2 content type line 23
ISSN:	1476-1122 1476-4660 1476-4660
DOI:	10.1038/nmat4519