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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:622.)
© 2003 American Heart Association, Inc.

Vascular Biology

Olive Oil and Red Wine Antioxidant Polyphenols Inhibit Endothelial Activation

Antiatherogenic Properties of Mediterranean Diet Phytochemicals

Maria Annunziata Carluccio; Luisa Siculella; Maria Assunta Ancora; Marika Massaro; Egeria Scoditti; Carlo Storelli; Francesco Visioli; Alessandro Distante; Raffaele De Caterina

From the C.N.R. Institute of Clinical Physiology (M.A.C., M.A.A., M.M, E.S., A.D.), Lecce; Department of Biology (L.S., C.S.), University of Lecce; Institute of Pharmacological Sciences (F.V), School of Pharmacy, University of Milan; and Chair of Cardiology (R.D.C.), "G. d’Annunzio" University, Chieti, Italy.

Correspondence to Raffaele De Caterina, MD, PhD Chair of Cardiology, "G. d’Annunzio" University - Chieti, c/o Ospedale S. Camillo de Lellis, Via Forlanini, 50, I-66100 Chieti, Italy. E-mail rdecater{at}unich.it

Objective— Epidemiology suggests that Mediterranean diets are associated with reduced risk of cardiovascular disease. Because monocyte adhesion to the endothelium is crucial in early atherogenesis, we evaluated whether typical olive oil and red wine polyphenols affect endothelial–leukocyte adhesion molecule expression and monocyte adhesion.

Methods and Results— Phytochemicals in olive oil and red wine, including oleuropein, hydroxytyrosol, tyrosol, elenolic acid, and resveratrol, with or without antioxidant activity, were incubated with human umbilical vein endothelial cells for 30 minutes, followed by co-incubation with bacterial lipopolysaccharide or cytokines to trigger adhesion molecule expression. At nutritionally relevant concentrations, only oleuropein, hydroxytyrosol, and resveratrol, possessing a marked antioxidant activity, reduced monocytoid cell adhesion to stimulated endothelium, as well as vascular cell adhesion molecule-1 (VCAM-1) mRNA and protein by Northern analysis and cell surface enzyme immunoassay. Reporter gene assays with deletional VCAM-1 promoter constructs indicated the relevance of nuclear factor-B, activator protein-1, and possibly GATA binding sites in mediating VCAM-1 transcriptional inhibition. The involvement of nuclear factor-B and activator protein-1 was finally demonstrated at electrophoretic mobility shift assays.

Conclusions— Olive oil and red wine antioxidant polyphenols at nutritionally relevant concentrations transcriptionally inhibit endothelial adhesion molecule expression, thus partially explaining atheroprotection from Mediterranean diets.

Key Words: atherosclerosis • adhesion molecules • VCAM-1 • polyphenols • Mediterranean diets

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