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

Identificador:  imarina:3647280

Handle: https://hdl.handle.net/20.500.11797/imarina3647280

Autores:  Catalán, U; de las Hazas, MCL; Piñol, C; Rubió, L; Motilva, MJ; Fernandez-Castillejo, S; Solà, R

Resumen:
The main aim of this work is to gain insight into the potential mechanisms of hydroxytyrosol (HT) and its main plasmatic 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 expression compared with the control group in the isolated aorta. Further in-vitro mechanistic assays revealed that both HT and HTmet could reduce the adhesion of Jurkat-T-lymphocytes to human aortic endothelial cells at 1-5 μM, significantly greater reductions being observed with HTmet. This process appeared to be regulated by the MAPK pathway through the inactivation of p38δ, JNK1-3, CREB, AKT3, p53 and P70 S6 Kinase. We concluded that supplementation with HT precursors from olive oil might attenuate the initial steps of atherosclerosis at a molecular level. The reduction of lymphocyte adhesion and the modulation of MAPK pathway by HTmet could explain this phenomenon.