BACKGROUND: A Mediterranean dietary pattern has been associated with a reduced risk of coronary heart disease, as well as a reduction of oxidative stress, but studies indicating possible interactions between food intake and inflammatory mediators production at specific sites are lacking. AIM OF THE STUDY: To assess the relationship between Mediterranean diet consumption and inflammatory related molecules production in coronary vessels.

METHODS: A previously reported Mediterranean-diet score was computed summing-up the quintiles of eight dietary components from a validated food frequency questionnaire in 24 patients with unstable angina. Tumor necrosis factor (TNF-alpha) and vascular cell adhesion molecule (VCAM-1) concentrations were measured in coronary sinus blood.

RESULTS: Both biomarkers showed an inverse association with the Mediterraneandiet score. The association between VCAM-1 and the Mediterranean-diet score had an adjusted beta coefficient of -35.1 ng/ml (95% coefficient interval, CI: -63.5 to -6.7). The adjusted beta coefficient using TNF-alpha as the dependent variable was -41.6 pg/ml (95 % CI: -76.2 to -7.1). The consumption of olive oil as a single item showed a significant inverse association, and a Mediterranean-diet score excluding olive oil was also inversely associated with TNF-alpha and VCAM-1 serum levels in coronary venous blood.

CONCLUSIONS: Adherence to a Mediterranean dietary pattern may protect against coronary artery wall production of inflammatory mediators. This finding could provide a novel mechanistic explanation for the recognized lower coronary risk associated with a Mediterranean diet.

Hyperhomocysteinemia is a recognized risk factor for vascular disease, but pathogenetic mechanisms involved in its vascular actions are largely unknown. Because VCAM-1 expression is crucial in monocyte adhesion and early atherogenesis, we evaluated the NF-kappaB-related induction of VCAM-1 by homocysteine (Hcy) and the possible inhibitory effect of dietary polyphenolic antioxidants, such as trans-resveratrol (RSV) and hydroxytyrosol (HT), which are known inhibitors of NF-kappaB-mediated VCAM-1 induction. In human umbilical vein endothelial cells (HUVEC), Hcy, at 100 micromol/l, but not cysteine, induced VCAM-1 expression at the protein and mRNA levels, as shown by enzyme immunoassay and Northern analysis, respectively. Transfection studies with deletional VCAM-1 promoter constructs demonstrated that the two tandem NF-kappaB motifs in the VCAM-1 promoter are necessary for Hcy-induced VCAM-1 gene expression. Hcy-induced NF-kappaB activation was confirmed by EMSA, as shown by the nuclear translocation of its p65 (RelA) subunit and the degradation of the inhibitors IkappaB-alpha and IkappaB-beta by Western analysis. Hcy also increased intracellular reactive oxygen species by NAD(P)H oxidase activation, as shown by the membrane translocation of its p47(phox) subunit. NF-kappaB inhibitors decreased Hcy-induced intracellular reactive oxygen species and VCAM-1 expression. Finally, we found that nutritionally relevant concentrations of RSV and HT, but not folate and vitamin B6, reduce (by>60% at 10(-6) mol/l) Hcy-induced VCAM-1 expression and monocytoid cell adhesion to the endothelium. These data indicate that pathophysiologically relevant Hcy concentrations induce VCAM-1 expression through a prooxidant mechanism involving NF-kappaB. Natural Mediterranean diet antioxidants can inhibit such activation, suggesting their possible therapeutic role in Hcy-induced vascular damage.

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-kappaB, activator protein-1, and possibly GATA binding sites in mediating VCAM-1 transcriptional inhibition. The involvement of nuclear factor-kappaB 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.