Interferons are pro-inflammatory cytokines in sheared-stressed human aortic valve endothelial cells
© 2021 by the authors.
| Autores: | , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2021 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/260790 |
| Acceso en línea: | http://hdl.handle.net/10261/260790 |
| Access Level: | acceso abierto |
| Palabra clave: | Valvular endothelial cells Interferons Monocyte adhesion Inflammation JAK/STAT |
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Interferons are pro-inflammatory cytokines in sheared-stressed human aortic valve endothelial cellsParra Izquierdo, IvánSánchez-Bayuela, TaniaLópez, JavierGómez, CristinaPérez-Riesgo, EnriqueSan Román, José AlbertoSánchez Crespo, MarianoYacoub, MagdiChester, Adrian H.García-Rodríguez, CarmenValvular endothelial cellsInterferonsMonocyte adhesionInflammationJAK/STAT© 2021 by the authors.Calcific aortic valve disease (CAVD) is an athero-inflammatory process. Growing evidence supports the inflammation-driven calcification model, mediated by cytokines such as interferons (IFNs) and tumor necrosis factor (TNF)-α. Our goal was investigating IFNs’ effects in human aortic valve endothelial cells (VEC) and the potential differences between aortic (aVEC) and ventricular (vVEC) side cells. The endothelial phenotype was analyzed by Western blot, qPCR, ELISA, monocyte adhesion, and migration assays. In mixed VEC populations, IFNs promoted the activation of signal transducers and activators of transcription-1 and nuclear factor-κB, and the subsequent up-regulation of pro-inflammatory molecules. Side-specific VEC were activated with IFN-γ and TNF-α in an orbital shaker flow system. TNF-α, but not IFN-γ, induced hypoxia-inducible factor (HIF)-1α stabilization or endothelial nitric oxide synthase downregulation. Additionally, IFN-γ inhibited TNF-α–induced migration of aVEC. Also, IFN-γ triggered cytokine secretion and adhesion molecule expression in aVEC and vVEC. Finally, aVEC were more prone to cytokine-mediated monocyte adhesion under multiaxial flow conditions as compared with uniaxial flow. In conclusion, IFNs promote inflammation and reduce TNF-α–mediated migration in human VEC. Moreover, monocyte adhesion was higher in inflamed aVEC sheared under multiaxial flow, which may be relevant to understanding the initial stages of CAVD.This research was funded by grants from Spanish Ministry of Economy and Competitiveness, co-funded by the European Social Fund FEDER (SAF2013-44521-R, SAF2017-83079-R, PID2020- 113751RB-I00); Junta de Castilla y León (BIO/VA47/14, BIO/VA36/15, CSI035P17, GRS1432/A/16, GRS2205/A/2020, VA175P20, and Programa Estratégico IBGM-Escalera de Excelencia Ref. CLU2019-02); Fundación Domingo Martínez; and the Instituto de Salud Carlos III (Spanish Ministry of Health PI14/00022, CIBERCV CB16/11/00260). I.P. and T.S.B., PhD fellows from Valladolid University-Banco de Santander. A.C. was funded by the Magdi Yacoub Institute.Multidisciplinary Digital Publishing InstituteMinisterio de Economía y Competitividad (España)Agencia Estatal de Investigación (España)Ministerio de Ciencia, Innovación y Universidades (España)Junta de Castilla y LeónCSIC-UVA - Instituto de Biología y Genética Molecular (IBGM)Fundación Domingo MartínezInstituto de Salud Carlos IIIMinisterio de Sanidad (España)Universidad de ValladolidBanco SantanderMagdi Yacoub InstituteConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2022202220212022info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/260790reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO//SAF2013-44521-Rinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2017-83079-Rinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-113751RB-I00http://dx.doi.org/10.3390/ijms221910605Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2607902026-05-22T06:33:51Z |
| dc.title.none.fl_str_mv |
Interferons are pro-inflammatory cytokines in sheared-stressed human aortic valve endothelial cells |
| title |
Interferons are pro-inflammatory cytokines in sheared-stressed human aortic valve endothelial cells |
| spellingShingle |
Interferons are pro-inflammatory cytokines in sheared-stressed human aortic valve endothelial cells Parra Izquierdo, Iván Valvular endothelial cells Interferons Monocyte adhesion Inflammation JAK/STAT |
| title_short |
Interferons are pro-inflammatory cytokines in sheared-stressed human aortic valve endothelial cells |
| title_full |
Interferons are pro-inflammatory cytokines in sheared-stressed human aortic valve endothelial cells |
| title_fullStr |
Interferons are pro-inflammatory cytokines in sheared-stressed human aortic valve endothelial cells |
| title_full_unstemmed |
Interferons are pro-inflammatory cytokines in sheared-stressed human aortic valve endothelial cells |
| title_sort |
Interferons are pro-inflammatory cytokines in sheared-stressed human aortic valve endothelial cells |
| dc.creator.none.fl_str_mv |
Parra Izquierdo, Iván Sánchez-Bayuela, Tania López, Javier Gómez, Cristina Pérez-Riesgo, Enrique San Román, José Alberto Sánchez Crespo, Mariano Yacoub, Magdi Chester, Adrian H. García-Rodríguez, Carmen |
| author |
Parra Izquierdo, Iván |
| author_facet |
Parra Izquierdo, Iván Sánchez-Bayuela, Tania López, Javier Gómez, Cristina Pérez-Riesgo, Enrique San Román, José Alberto Sánchez Crespo, Mariano Yacoub, Magdi Chester, Adrian H. García-Rodríguez, Carmen |
| author_role |
author |
| author2 |
Sánchez-Bayuela, Tania López, Javier Gómez, Cristina Pérez-Riesgo, Enrique San Román, José Alberto Sánchez Crespo, Mariano Yacoub, Magdi Chester, Adrian H. García-Rodríguez, Carmen |
| author2_role |
author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Ministerio de Economía y Competitividad (España) Agencia Estatal de Investigación (España) Ministerio de Ciencia, Innovación y Universidades (España) Junta de Castilla y León CSIC-UVA - Instituto de Biología y Genética Molecular (IBGM) Fundación Domingo Martínez Instituto de Salud Carlos III Ministerio de Sanidad (España) Universidad de Valladolid Banco Santander Magdi Yacoub Institute Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72] |
| dc.subject.none.fl_str_mv |
Valvular endothelial cells Interferons Monocyte adhesion Inflammation JAK/STAT |
| topic |
Valvular endothelial cells Interferons Monocyte adhesion Inflammation JAK/STAT |
| description |
© 2021 by the authors. |
| publishDate |
2021 |
| dc.date.none.fl_str_mv |
2021 2022 2022 2022 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article http://purl.org/coar/resource_type/c_6501 Publisher's version info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10261/260790 |
| url |
http://hdl.handle.net/10261/260790 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
#PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# info:eu-repo/grantAgreement/MINECO//SAF2013-44521-R info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2017-83079-R info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-113751RB-I00 http://dx.doi.org/10.3390/ijms221910605 Sí |
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info:eu-repo/semantics/openAccess |
| eu_rights_str_mv |
openAccess |
| dc.publisher.none.fl_str_mv |
Multidisciplinary Digital Publishing Institute |
| publisher.none.fl_str_mv |
Multidisciplinary Digital Publishing Institute |
| dc.source.none.fl_str_mv |
reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC instname:Consejo Superior de Investigaciones Científicas (CSIC) |
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Consejo Superior de Investigaciones Científicas (CSIC) |
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DIGITAL.CSIC. Repositorio Institucional del CSIC |
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DIGITAL.CSIC. Repositorio Institucional del CSIC |
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1869425488609411072 |
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15,811543 |