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

J.D. Hutcheson, C. Goettsch, S. Bertazzo, N. Maldonado, J.L. Ruiz, W. Goh, K. Yabusaki, T. Faits, C.V.C. Bouten, G. Franck, T. Quillard, P. Libby, M. Aikawa, S. Weinbaum, E. Aikawa

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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.

Original languageEnglish
Pages (from-to)335-343
Number of pages9
JournalNature Materials
Volume15
Issue number3
DOIs
Publication statusPublished - 1 Mar 2016

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    Hutcheson, J. D., Goettsch, C., Bertazzo, S., Maldonado, N., Ruiz, J. L., Goh, W., Yabusaki, K., Faits, T., Bouten, C. V. C., Franck, G., Quillard, T., Libby, P., Aikawa, M., Weinbaum, S., & Aikawa, E. (2016). Genesis and growth of extracellular-vesicle-derived microcalcification in atherosclerotic plaques. Nature Materials, 15(3), 335-343. https://doi.org/10.1038/nmat4519