气候变化领域集成服务门户(CCPortal): Nanoanalytical analysis of bisphosphonate-driven alterations of microcalcifications using a 3D hydrogel system and in vivo mouse model

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DOI	10.1073/pnas.1811725118
	Nanoanalytical analysis of bisphosphonate-driven alterations of microcalcifications using a 3D hydrogel system and in vivo mouse model
	Ruiz J.L.; Hutcheson J.D.; Cardoso L.; Nik A.B.; de Abreu A.C.; Pham T.; Buffolo F.; Busatto S.; Federici S.; Ridolfi A.; Aikawa M.; Bertazzo S.; Bergese P.; Weinbaum S.; Aikawa E.
发表日期	2021
ISSN	00278424
卷号	118 期号:14
英文摘要	Vascular calcification predicts atherosclerotic plaque rupture and cardiovascular events. Retrospective studies of women taking bisphosphonates (BiPs), a proposed therapy for vascular calcification, showed that BiPs paradoxically increased morbidity in patients with prior acute cardiovascular events but decreased mortality in event-free patients. Calcifying extracellular vesicles (EVs), released by cells within atherosclerotic plaques, aggregate and nucleate calcification. We hypothesized that BiPs block EV aggregation and modify existing mineral growth, potentially altering microcalcification morphology and the risk of plaque rupture. Three-dimensional (3D) collagen hydrogels incubated with calcifying EVs were used to mimic fibrous cap calcification in vitro, while an ApoE-/- mouse was used as a model of atherosclerosis in vivo. EV aggregation and formation of stress-inducing microcalcifications was imaged via scanning electron microscopy (SEM) and atomic force microscopy (AFM). In both models, BiP (ibandronate) treatment resulted in time-dependent changes in microcalcification size and mineral morphology, dependent on whether BiP treatment was initiated before or after the expected onset of microcalcification formation. Following BiP treatment at any time, microcalcifications formed in vitro were predicted to have an associated threefold decrease in fibrous cap tensile stress compared to untreated controls, estimated using finite element analysis (FEA). These findings support our hypothesis that BiPs alter EV-driven calcification. The study also confirmed that our 3D hydrogel is a viable platform to study EVmediated mineral nucleation and evaluate potential therapies for cardiovascular calcification. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Atherosclerosis; Bisphosphonate; Extracellular vesicles; Microcalcification
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179959
作者单位	Center for Interdisciplinary Cardiovascular Sciences, Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States; Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, United States; Department of Biomedical Engineering, Florida International University, Miami, FL 33174, United States; Department of Biomedical Engineering, City College of New York, New York, NY 10031, United States; Department of Medical Physics and Biomedical Engineering, University College London, London, WC1E 6BT, United Kingdom; Vascular Biology Program, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, United States; Department of Molecular and Translational Medicine, University of Brescia, Brescia, 25123, Italy; Department of Mechanical and Industrial Engineering, National Interuniversity Consortium of Materials Science and Technology, University of Brescia, Brescia, 25123, Italy; Consorzio Interuniversitario per lo...
推荐引用方式 GB/T 7714	Ruiz J.L.,Hutcheson J.D.,Cardoso L.,et al. Nanoanalytical analysis of bisphosphonate-driven alterations of microcalcifications using a 3D hydrogel system and in vivo mouse model[J],2021,118(14).
APA	Ruiz J.L..,Hutcheson J.D..,Cardoso L..,Nik A.B..,de Abreu A.C..,...&Aikawa E..(2021).Nanoanalytical analysis of bisphosphonate-driven alterations of microcalcifications using a 3D hydrogel system and in vivo mouse model.Proceedings of the National Academy of Sciences of the United States of America,118(14).
MLA	Ruiz J.L.,et al."Nanoanalytical analysis of bisphosphonate-driven alterations of microcalcifications using a 3D hydrogel system and in vivo mouse model".Proceedings of the National Academy of Sciences of the United States of America 118.14(2021).