Microvesicles from indoxyl sulfate-treated endothelial cells induce vascular calcification in vitro
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 ide...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-01-01
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| Series: | Computational and Structural Biotechnology Journal |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2001037020300295 |
| _version_ | 1818970281594585088 |
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| author | Matilde Alique Guillermo Bodega Elena Corchete Estefanya García-Menéndez Patricia de Sequera Rafael Luque Daily Rodríguez-Padrón María Marqués José Portolés Julia Carracedo Rafael Ramírez |
| author_facet | Matilde Alique Guillermo Bodega Elena Corchete Estefanya García-Menéndez Patricia de Sequera Rafael Luque Daily Rodríguez-Padrón María Marqués José Portolés Julia Carracedo Rafael Ramírez |
| author_sort | Matilde Alique |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T14:33:59Z |
| format | Article |
| id | doaj.art-8699c88c95d945f49e905f35100260d2 |
| institution | Directory Open Access Journal |
| issn | 2001-0370 |
| language | English |
| last_indexed | 2024-12-20T14:33:59Z |
| publishDate | 2020-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Computational and Structural Biotechnology Journal |
| spelling | doaj.art-8699c88c95d945f49e905f35100260d22022-12-21T19:37:31ZengElsevierComputational and Structural Biotechnology Journal2001-03702020-01-0118953966Microvesicles from indoxyl sulfate-treated endothelial cells induce vascular calcification in vitroMatilde Alique0Guillermo Bodega1Elena Corchete2Estefanya García-Menéndez3Patricia de Sequera4Rafael Luque5Daily Rodríguez-Padrón6María Marqués7José Portolés8Julia Carracedo9Rafael Ramírez10Departamento de Biología de Sistemas, Universidad de Alcalá (IRYCIS), Alcalá de Henares, Madrid, Spain; Corresponding authors at: Universidad de Alcalá (IRYCIS), Facultad de Medicina y Ciencias de las Salud. Departamento Biología de Sistemas, E-28871, Alcalá de Henares, Madrid, Spain (M. Alique).Departamento de Biomedicina y Biotecnología, Universidad de Alcalá, Alcalá de Henares, Madrid, SpainSección de Nefrología, Hospital Universitario Infanta Leonor, Madrid, SpainServicio Nefrología, Hospital Universitario Puerta de Hierro, Madrid, SpainSección de Nefrología, Hospital Universitario Infanta Leonor, Madrid, SpainDepartamento de Química Orgánica, Universidad de Córdoba, Edificio Marie Curie (C-3), Carretera Nacional IV-A, Km 396, Córdoba, SpainDepartamento de Química Orgánica, Universidad de Córdoba, Edificio Marie Curie (C-3), Carretera Nacional IV-A, Km 396, Córdoba, SpainServicio Nefrología, Hospital Universitario Puerta de Hierro, Madrid, SpainServicio Nefrología, Hospital Universitario Puerta de Hierro, Madrid, SpainDepartamento de Genética, Fisiología y Microbiología, Facultad de Ciencias Biológicas, Universidad Complutense de Madrid/ Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain; Corresponding authors at: Universidad de Alcalá (IRYCIS), Facultad de Medicina y Ciencias de las Salud. Departamento Biología de Sistemas, E-28871, Alcalá de Henares, Madrid, Spain (M. Alique).Departamento de Biología de Sistemas, Universidad de Alcalá (IRYCIS), Alcalá de Henares, Madrid, SpainVascular 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.http://www.sciencedirect.com/science/article/pii/S2001037020300295MicrovesiclesUremic toxinsEndothelial cellsVascular cellsCalcification |
| spellingShingle | Matilde Alique Guillermo Bodega Elena Corchete Estefanya García-Menéndez Patricia de Sequera Rafael Luque Daily Rodríguez-Padrón María Marqués José Portolés Julia Carracedo Rafael Ramírez Microvesicles from indoxyl sulfate-treated endothelial cells induce vascular calcification in vitro Computational and Structural Biotechnology Journal Microvesicles Uremic toxins Endothelial cells Vascular cells Calcification |
| title | Microvesicles from indoxyl sulfate-treated endothelial cells induce vascular calcification in vitro |
| title_full | Microvesicles from indoxyl sulfate-treated endothelial cells induce vascular calcification in vitro |
| title_fullStr | Microvesicles from indoxyl sulfate-treated endothelial cells induce vascular calcification in vitro |
| title_full_unstemmed | Microvesicles from indoxyl sulfate-treated endothelial cells induce vascular calcification in vitro |
| title_short | Microvesicles from indoxyl sulfate-treated endothelial cells induce vascular calcification in vitro |
| title_sort | microvesicles from indoxyl sulfate treated endothelial cells induce vascular calcification in vitro |
| topic | Microvesicles Uremic toxins Endothelial cells Vascular cells Calcification |
| url | http://www.sciencedirect.com/science/article/pii/S2001037020300295 |
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