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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Detalles Bibliográficos
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
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2018
País:España
Institución:Universitat de Lleida (UdL)
Repositorio:Repositori Obert UdL
OAI Identifier:oai:repositori.udl.cat:10459.1/71571
Acceso en línea:https://doi.org/10.1016/j.jff.2017.11.007
http://hdl.handle.net/10459.1/71571
Access Level:acceso abierto
Palabra clave:Hydroxytyrosol
Hydroxytyrosol metabolites
Atherosclerosis
ApoE−/−mice
Human aortic endothelial cells
Descripción
Sumario: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.