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Journal of Biochemistry Advance Access originally published online on July 27, 2006
Journal of Biochemistry 2006 140(3):383-391; doi:10.1093/jb/mvj166
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© 2006 The Japanese Biochemical Society.

ARTICLE

Hydroxytyrosol Administration Enhances Atherosclerotic Lesion Development in Apo E Deficient Mice

Sergio Acín1,*, María A. Navarro1,*, José M. Arbonés-Mainar1, Natalia Guillén1, Alfonso J. Sarría1, Ricardo Carnicer1, Joaquín C. Surra1, Israel Orman2, Jose C. Segovia2, Rafael de la Torre3, María-Isabel Covas3, Juan Fernández-Bolaños4, Valentina Ruiz-Gutiérrez4 and Jesús Osada1,{dagger}

1 Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Veterinaria, Universidad de Zaragoza; 2 Departamento de Terapia Génica de la Hematopoyesis, CEIMAT, Madrid; 3 Instituto Municipal de Investigaciones Médicas de Barcelona; and 4 Instituto de la Grasa, Sevilla, Spain

* To whom correspondence should be addressed at: Department of Biochemistry and Molecular Biology, Veterinary School, University of Zaragoza, Miguel Servet, 177, E-50013 Zaragoza, Spain. Tel: +34-976-761-644, Fax: +34-976-761-612, E-mail: Josada{at}unizar.es

Hydroxytyrosol is a phenol found in olive oil. To verify the effect of hydroxytyrosol on the development of atherosclerosis, two groups of apo E deficient male mice on a standard chow diet were used: the control group receiving only water, and the second group an aqueous solution of hydroxytyrosol in order to provide a dose of 10 mg/kg/day to each mouse. This treatment was maintained for 10 weeks. At the moment of sacrifice, blood was drawn and heart removed. Plasma lipids, apolipoproteins and monocyte Mac-1 expression were assayed as well as aortic atherosclerotic areas in both groups. Data showed no significant changes in HDL cholesterol, paraoxonase, apolipoprotein B or triglyceride levels. However, hydroxytyrosol administration decreased apolipoprotein A-I and increased total cholesterol, atherosclerotic lesion areas and circulating monocytes expressing Mac-1. The latter was highly correlated with lesion areas (r = 0.65, P < 0.01). These results indicate that administration of hydroxytyrosol in low cholesterol diets increases atherosclerotic lesion associated with the degree of monocyte activation and remodelling of plasma lipoproteins. Our data supports the concept that phenolic-enriched products, out of the original matrix, could be not only non useful but also harmful. Our results suggest that the formulation of possible functional foods should approximate as much as possible the natural environment in which active molecules are found.

* Both authors contributed equally to this manuscript.


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