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Genesis and growth of extracellular-vesicle-derived microcalcification inatherosclerotic plaques

Genesis and growth of extracellular-vesicle-derived microcalcification inatherosclerotic 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 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nature Materials Springer Journals

Genesis and growth of extracellular-vesicle-derived microcalcification inatherosclerotic plaques

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References (53)

Publisher
Springer Journals
Copyright
Copyright © 2016 by Nature Publishing Group
Subject
Materials Science; Materials Science, general; Optical and Electronic Materials; Biomaterials; Nanotechnology; Condensed Matter Physics
ISSN
1476-1122
eISSN
1476-4660
DOI
10.1038/nmat4519
Publisher site
See Article on Publisher Site

Abstract

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.

Journal

Nature Materials – Springer Journals

Published: Jan 11, 2016

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