S-EPMC4767675 - Genesis and growth of extracellular-vesicle-derived microcalcification in atherosclerotic plaques. - OmicsDI

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

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.

SUBMITTER: Hutcheson JD

PROVIDER: S-EPMC4767675 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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

Hutcheson Joshua D JD Goettsch Claudia C Bertazzo Sergio S Maldonado Natalia N Ruiz Jessica L JL Goh Wilson W Yabusaki Katsumi K Faits Tyler T Bouten Carlijn C Franck Gregory G Quillard Thibaut T Libby Peter P Aikawa Masanori M Weinbaum Sheldon S Aikawa Elena E

Nature materials 20160111 3

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 ...[more]

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