Protection of LDL from oxidation by olive oil polyphenols is associated with a downregulation of CD40-ligand expression and its downstream products in vivo in humans123

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Background: Recently, the European Food Safety Authority approved a claim concerning the benefits of olive oil polyphenols for the protection of LDL from oxidation. Polyphenols could exert health benefits not only by scavenging free radicals but also by modulating gene expression.

Objective: We assessed whether olive oil polyphenols could modulate the human in vivo expressions of atherosclerosis-related genes in which LDL oxidation is involved.

Design: In a randomized, crossover, controlled trial, 18 healthy European volunteers daily received 25 mL olive oil with a low polyphenol content (LPC: 2.7 mg/kg) or a high polyphenol content (HPC: 366 mg/kg) in intervention periods of 3 wk separated by 2-wk washout periods.

Results: Systemic LDL oxidation and monocyte chemoattractant protein 1 and the expression of proatherogenic genes in peripheral blood mononuclear cells [ie, CD40 ligand (CD40L), IL-23α subunit p19 (IL23A), adrenergic β-2 receptor (ADRB2), oxidized LDL (lectin-like) receptor 1 (OLR1), and IL-8 receptor-α (IL8RA)] decreased after the HPC intervention compared with after the LPC intervention. Random-effects linear regression analyses showed 1) a significant decrease in CD40, ADRB2, and IL8RA gene expression with the decrease of LDL oxidation and 2) a significant decrease in intercellular adhesion molecule 1 and OLR1 gene expression with increasing concentrations of tyrosol and hydroxytyrosol in urine.

Conclusions: In addition to reducing LDL oxidation, the intake of polyphenol-rich olive oil reduces CD40L gene expression, its downstream products, and related genes involved in atherogenic and inflammatory processes in vivo in humans. These findings provide evidence that polyphenol-rich olive oil can act through molecular mechanisms to provide cardiovascular health benefits. This trial was registered at www.controlled-trials.com as ISRCTN09220811.

Abbreviations:

CD40L
CD40 ligand
HPC
high polyphenol content
ICAM1
intercellular adhesion molecule 1
IFN-γ
interferon γ
LPC
low polyphenol content
MCP1
monocyte chemoattractant protein 1
PBMC
peripheral blood mononuclear cell

Cited by (0)

1

From the Cardiovascular Risk and Nutrition (OC, M-IC, DM-A, JV, and MF) and Human Pharmacology and Clinical Neurosciences (OK and RdlT) Research Groups of Institut Mar d’Investigacions Mèdiques (IMIM)–Research Institute Hospital del Mar; CIBER de Fisiopatología de la Obesidad y Nutrición (OC, M-IC, DM-A, MF, RdlT), Barcelona, Spain; the Program of Medicine, University of Barcelona, Barcelona, Spain (OC); the Research Institute of Public Health, University of Eastern Finland, Kuopio, Finland (KN); the Hellenic Health Foundation, Athens, Greece (VK); and the German Institute of Human Nutrition, Postdam-Rehbruecke, Germany (H-FZ).

2

Supported by the European Union (grant QLK1-CT-2001-00287) and Ministerio de Ciencia e Innovacio´n/Fondos Europeos de Desarrollo Regional (grant AGL2009-13517-C03-01) and in part by the Instituto de Salud Carlos III (Sistema Nacional de Salud contract Miguel Servet CP06/00100 and Rio Hortega CM08/00054).

3

Address correspondence to M Fito´, Cardiovascular Risk and Nutrition Research Group, IMIM–Research Institute Hospital del Mar, Barcelona Biomedical Research Park, Carrer Doctor Aiguader, 88, 08003 Barcelona, Spain. E-mail: [email protected].

Copyright © 2012 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.