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

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Early atherosclerosis features functional and structural changes in the endothelial barrier function that affect the traffic of molecules and solutes between the vessel lumen and the vascular wall. Such changes are mechanistically related to the development of atherosclerosis. Proatherogenic stimuli and cardiovascular risk factors, such as dyslipidaemias, diabetes, obesity, and smoking, all increase endothelial permeability sharing a common signalling denominator: an imbalance in the production/disposal of reactive oxygen species (ROS), broadly termed oxidative stress. Mostly as a consequence of the activation of enzymatic systems leading to ROS overproduction, proatherogenic factors lead to a pro-inflammatory status that translates in changes in gene expression and functional rearrangements, including changes in the transendothelial transport of molecules, leading to the deposition of low-density lipoproteins (LDL) and the subsequent infiltration of circulating leucocytes in the intima. In this review, we focus on such early changes in atherogenesis and on the concept that proatherogenic stimuli and risk factors for cardiovascular disease, by altering the endothelial barrier properties, co-ordinately trigger the accumulation of LDL in the intima and ultimately plaque formation.

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In the human vascular endothelium, statins reduce COX-2 and MMP-9 expression and activity. Through this mechanism, statins exert an anti-angiogenic effect possibly contributing to the cholesterol-lowering-unrelated protective effects of statins against plaque inflammatory angiogenesis and rupture.

Epidemiological and clinical studies found that the traditional Mediterranean-style diet is associated with significantly lower mortality from coronary artery disease. Although it is difficult to isolate individual dietary factors, cumulative evidence suggests that olive oil, used as primary source of fat by Mediterranean populations, may play a key role in the observed cardiovascular benefit. Olive oil is a priceless source of vitamins and polyphenolic antioxidants, and has a balanced ratio of monounsaturated and polyunsaturated fatty acids. There are multiple mechanisms by which olive oil might impact the development of atherosclerosis. Olive oil decreases LDL-cholesterol and increases HDL-cholesterol, and also reduces oxidative stress due to polyphenols, which are able to scavenge free radicals and protect LDL from oxidation. In addition, olive oil components may interfere with the inflammatory response within atherosclerotic lesion, by inhibiting endothelial activation involved in monocyte recruitment during early atherogenesis and macrophage production of inflammatory cytokines and matrix degrading enzymes, thus improving vascular stability. Other vasculoprotective mechanisms by olive oil components derive from anti-thrombotic and anti-hypertensive actions. The available data support the need to preserve certain dietary traditions, such as olive oil consumption, to counteract the burden of cardiovascular disease.

SUMMARYNutraceuticals are potentially healthful foods that play a role in maintaining human well being, enhancing health and preventing, or even treating, specific diseases. More than for any other diseases, cardiovascular diseases occur in association with risk factors that are amenable to prevention or treatment by nutraceutical interventions. Several ingredients marketed for use in dietary supplements address such risk factors. The ability of nutraceuticals to favorably influence cardiovascular risk factors and atherosclerotic vascular disease should be recognized as an enormous opportunity for the prevention or treatment of this common condition. In this review, we attempt at summarizing some of the recent research findings on ω-3-polyunsaturated fatty acids and antioxidant polyphenols that have beneficial cardiovascular effects to update the practicing clinicians on the potential benefits of nutraceuticals in this area."Let food be thy medicine and medicine be thy food" Hyppocrates (460-377 B.C.)