Microvesicles from indoxyl sulfate-treated endothelial cells induce vascular calcification in vitro

Authors
Alique Aguilar, MatildeUniversity of Alcalá Author; Bodega Magro, GuillermoUniversity of Alcalá Author; Corchete Prats, Elena de la AsunciónUniversity of Alcalá Author; García Menéndez, Estefanya; Sequera Ortiz, Patricia deUniversity of Alcalá Author; [et al.]
Identifiers
Permanent link (URI): http://hdl.handle.net/10017/51271
DOI: 10.1016/j.csbj.2020.04.006
ISSN: 2001-0370
Date
2020-04-01
Affiliation
Universidad de Alcalá. Departamento de Biomedicina y Biotecnología; Universidad de Alcalá. Departamento de Biología de Sistemas
Funders
Instituto de Salud Carlos III
Sociedad Española de Nefrología
Universidad de Alcalá
Grupo Santander
University fo California San Diego
Bibliographic citation
Alique, M., Bodega, G., Corchete, E., García-Menéndez, E., De Sequera, P., Luque, R., . . . Ramírez, R. (2020). Microvesicles from indoxyl sulfate-treated endothelial cells induce vascular calcification in vitro. Computational and Structural Biotechnology Journal, 18, 953-966.
Keywords
Microvesicles
Uremic toxins
Endothelial cells
Vascular cells
Calcification
Project
info:eu-repo/grantAgreement/ISCIII/PI19%2F00240
info:eu-repo/grantAgreement/ISCIII/PI19%2F01029
info:eu-repo/grantAgreement/Santander%2FUCM//PR41%2F17-20964
info:eu-repo/grantAgreement/UAH//GP-2018-4
info:eu-repo/grantAgreement/UAH//CGC2018%2FBIO-010
info:eu-repo/grantAgreement/UCSD//P30AR073761
Document type
info:eu-repo/semantics/article
Version
info:eu-repo/semantics/publishedVersion
Rights
© 2020 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology
Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
Access rights
info:eu-repo/semantics/openAccess
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Abstract
Vascular calcification (VC), an unpredictable pathophysiological process and critical event in patients with cardiovascular diseases (CVDs), is the leading cause of morbi-mortality and disability in chronic kidney disease (CKD) patients worldwide. Currently, no diagnostic method is available for identifying patients at risk of VC development; the pathology is detected when the process is irreversible. Extracellular vesicles (EVs) from endothelial cells might promote VC. Therefore, their evaluation and characterization could be useful for designing new diagnostic tools. The aim of the present study is to investigate whether microvesicles (MVs) from endothelial cells damaged by uremic toxin and indoxyl sulfate (IS) could induce calcification in human vascular smooth muscle cells (VMSCs). Besides, we have also analyzed the molecular mechanisms by which these endothelial MVs can promote VC development. Endothelial damage has been evaluated according to the percentage of senescence in endothelial cells, differential microRNAs in endothelial cells, and the amount of MVs released per cell. To identify the role of MVs in VC, VSMCs were treated with MVs from IS-treated endothelial cells. Calcium, inflammatory gene expression, and procalcification mediator levels in VSMCs were determined. IS-treated endothelial cells underwent senescence and exhibited modulated microRNA expression and an increase in the release of MVs. VSMCs exposed to these MVs modulated the expression of pro-inflammatory genes and some mediators involved in calcification progression. MVs produced by IS-treated endothelial cells promoted calcification in VSMCs.
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© 2020 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology
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