Hydroxytyrosol and its main plasma circulating metabolites attenuate the initial steps of atherosclerosis through inhibition of the MAPK pathway

The main aim of this work is to gain insight into the potential mechanisms of hydroxytyrosol (HT) and its mainplasmatic metabolites (HTmet) that improve the endothelial function. Feeding ApoE−/−mice with 10 mg/kg/day of HT derivatives for 12 weeks significantly reduced E-selectin, VCAM-1, MCP-1, ICA...

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Autores: Catalán Santos, Úrsula, López de las Hazas Mingo, María del Carmen, Piñol Felis, Carme, Rubió Piqué, Laura, Motilva Casado, Mª José, Fernández Castillejo, Sara, Solà, Rosa
Formato: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2018
País:España
Recursos:Universitat de Lleida (UdL)
Repositorio:Repositori Obert UdL
OAI Identifier:oai:repositori.udl.cat:10459.1/71571
Acesso em linha:https://doi.org/10.1016/j.jff.2017.11.007
http://hdl.handle.net/10459.1/71571
Access Level:acceso abierto
Palavra-chave:Hydroxytyrosol
Hydroxytyrosol metabolites
Atherosclerosis
ApoE−/−mice
Human aortic endothelial cells
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spelling Hydroxytyrosol and its main plasma circulating metabolites attenuate the initial steps of atherosclerosis through inhibition of the MAPK pathwayCatalán Santos, ÚrsulaLópez de las Hazas Mingo, María del CarmenPiñol Felis, CarmeRubió Piqué, LauraMotilva Casado, Mª JoséFernández Castillejo, SaraSolà, RosaHydroxytyrosolHydroxytyrosol metabolitesAtherosclerosisApoE−/−miceHuman aortic endothelial cellsThe main aim of this work is to gain insight into the potential mechanisms of hydroxytyrosol (HT) and its mainplasmatic metabolites (HTmet) that improve the endothelial function. Feeding ApoE−/−mice with 10 mg/kg/day of HT derivatives for 12 weeks significantly reduced E-selectin, VCAM-1, MCP-1, ICAM-1, and F4/80 ex-pression compared with the control group in the isolated aorta. Furtherin-vitromechanistic assays revealed thatboth HT and HTmet could reduce the adhesion of Jurkat-T-lymphocytes to human aortic endothelial cells at1–5 μM, significantly greater reductions being observed with HTmet. This process appeared to be regulated bythe MAPK pathway through the inactivation of p38δ, JNK1-3, CREB, AKT3, p53 and P70 S6 Kinase. We con-cluded that supplementation with HT precursors from olive oil might attenuate the initial steps of atherosclerosisat a molecular level. The reduction of lymphocyte adhesion and the modulation of MAPK pathway by HTmetcould explain this phenomenon.This work was partly supported by state grant: The MEFOPC Project (Subprojects AGL2012-40144-C03-02 and AGL2012-40144-C03-03) from the Spanish Ministry of Education and Science (Ministerio de Educación y Ciencia). We wish to acknowledge the support of the Institut d’Investigació Sanitària Pere Virgili (IISPV) and the EURECAT-Centre Tecnològic de Nutrició i Salut (CTNS), Reus, Spain and the University of Lleida through the M-C. López de las Hazas grant and the L. Rubió Sara Borrell postdoctoral grant (CD14/00275). And the Ú. Catalán Pla estratègic de recerca i innovació en salut (PERIS) post-doctoral grant (SLT002/16/00239; Catalunya, Spain). NFOC-Salut group is a consolidated research group of Generalitat de Catalunya, Spain (2014 SGR 873).Elsevier2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttps://doi.org/10.1016/j.jff.2017.11.007http://hdl.handle.net/10459.1/71571reponame:Repositori Obert UdL instname:Universitat de Lleida (UdL)Inglésinfo:eu-repo/grantAgreement/MINECO//AGL2012-40144-C03-02info:eu-repo/grantAgreement/MINECO//AGL2012-40144-C03-03Versió postprint del document publicat a: https://doi.org/10.1016/j.jff.2017.11.007Journal of Functional Foods, 2018, vol. 40, p. 280-291cc-by-nc-nd, (c) Elsevier, 2018info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-nd/4.0/oai:repositori.udl.cat:10459.1/715712026-06-24T12:42:17Z
dc.title.none.fl_str_mv Hydroxytyrosol and its main plasma circulating metabolites attenuate the initial steps of atherosclerosis through inhibition of the MAPK pathway
title Hydroxytyrosol and its main plasma circulating metabolites attenuate the initial steps of atherosclerosis through inhibition of the MAPK pathway
spellingShingle Hydroxytyrosol and its main plasma circulating metabolites attenuate the initial steps of atherosclerosis through inhibition of the MAPK pathway
Catalán Santos, Úrsula
Hydroxytyrosol
Hydroxytyrosol metabolites
Atherosclerosis
ApoE−/−mice
Human aortic endothelial cells
title_short Hydroxytyrosol and its main plasma circulating metabolites attenuate the initial steps of atherosclerosis through inhibition of the MAPK pathway
title_full Hydroxytyrosol and its main plasma circulating metabolites attenuate the initial steps of atherosclerosis through inhibition of the MAPK pathway
title_fullStr Hydroxytyrosol and its main plasma circulating metabolites attenuate the initial steps of atherosclerosis through inhibition of the MAPK pathway
title_full_unstemmed Hydroxytyrosol and its main plasma circulating metabolites attenuate the initial steps of atherosclerosis through inhibition of the MAPK pathway
title_sort Hydroxytyrosol and its main plasma circulating metabolites attenuate the initial steps of atherosclerosis through inhibition of the MAPK pathway
dc.creator.none.fl_str_mv Catalán Santos, Úrsula
López de las Hazas Mingo, María del Carmen
Piñol Felis, Carme
Rubió Piqué, Laura
Motilva Casado, Mª José
Fernández Castillejo, Sara
Solà, Rosa
author Catalán Santos, Úrsula
author_facet Catalán Santos, Úrsula
López de las Hazas Mingo, María del Carmen
Piñol Felis, Carme
Rubió Piqué, Laura
Motilva Casado, Mª José
Fernández Castillejo, Sara
Solà, Rosa
author_role author
author2 López de las Hazas Mingo, María del Carmen
Piñol Felis, Carme
Rubió Piqué, Laura
Motilva Casado, Mª José
Fernández Castillejo, Sara
Solà, Rosa
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Hydroxytyrosol
Hydroxytyrosol metabolites
Atherosclerosis
ApoE−/−mice
Human aortic endothelial cells
topic Hydroxytyrosol
Hydroxytyrosol metabolites
Atherosclerosis
ApoE−/−mice
Human aortic endothelial cells
description The main aim of this work is to gain insight into the potential mechanisms of hydroxytyrosol (HT) and its mainplasmatic metabolites (HTmet) that improve the endothelial function. Feeding ApoE−/−mice with 10 mg/kg/day of HT derivatives for 12 weeks significantly reduced E-selectin, VCAM-1, MCP-1, ICAM-1, and F4/80 ex-pression compared with the control group in the isolated aorta. Furtherin-vitromechanistic assays revealed thatboth HT and HTmet could reduce the adhesion of Jurkat-T-lymphocytes to human aortic endothelial cells at1–5 μM, significantly greater reductions being observed with HTmet. This process appeared to be regulated bythe MAPK pathway through the inactivation of p38δ, JNK1-3, CREB, AKT3, p53 and P70 S6 Kinase. We con-cluded that supplementation with HT precursors from olive oil might attenuate the initial steps of atherosclerosisat a molecular level. The reduction of lymphocyte adhesion and the modulation of MAPK pathway by HTmetcould explain this phenomenon.
publishDate 2018
dc.date.none.fl_str_mv 2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://doi.org/10.1016/j.jff.2017.11.007
http://hdl.handle.net/10459.1/71571
url https://doi.org/10.1016/j.jff.2017.11.007
http://hdl.handle.net/10459.1/71571
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/MINECO//AGL2012-40144-C03-02
info:eu-repo/grantAgreement/MINECO//AGL2012-40144-C03-03
Versió postprint del document publicat a: https://doi.org/10.1016/j.jff.2017.11.007
Journal of Functional Foods, 2018, vol. 40, p. 280-291
dc.rights.none.fl_str_mv cc-by-nc-nd, (c) Elsevier, 2018
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
rights_invalid_str_mv cc-by-nc-nd, (c) Elsevier, 2018
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repositori Obert UdL
instname:Universitat de Lleida (UdL)
instname_str Universitat de Lleida (UdL)
reponame_str Repositori Obert UdL
collection Repositori Obert UdL
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869409506327265280
score 15,811543

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