期刊
NATURE MATERIALS
卷 15, 期 3, 页码 335-+出版社
NATURE PORTFOLIO
DOI: 10.1038/nmat4519
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资金
- Kowa Company
- National Institutes of Health [R01HL114805, R01HL109506]
- Harvard Catalyst Advanced Microscopy Pilot Award
- Harvard Clinical and hfranslational Science Center (National Center for Research Resources)
- Harvard Clinical and hfranslational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health) [TR001102]
- Harvard University
- Imperial College London
- [R0111L80472]
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.
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