FIGURE 12.8 Olive oil antioxidant polyphenols decrease monocytoid cell adhesion to HUVEC. U937 cells added in suspension to HUVEC do not normally adhere to unstimulated monolayers and are easily removed with washing (control, no stimulation), while adhesion is dramatically increased by the addition of LPS (1 |mmol/L). U937 cell adhesion is reduced about 50% (lower panels) in HUVEC treated with hydroxytyrosol and oleuropein at 15 |mmol/L for 30 min and then stimulated with LPS. Cell counts shown (mean ± SD, n = 6 for each condition) within a grid area at high power field (0.16 mm2). This experiment was repeated four times with similar results.

Because VCAM-1 is the adhesion molecule principally and specifically involved in the initiation and progression of atherosclerotic lesions,55 we focused our interest on its modulation by olive oil polyphenols. We assessed and compared the inhibition of stimulated VCAM-1 expression by polyphenols in response to structurally unrelated agonists such as LPS, cytokines, and PMA, which served as a stimulus for endothelial activation that bypasses membrane receptors. We observed that both oleuropein and hydroxytyrosol inhibited stimulated VCAM-1 expression to the same extent with all stimuli, independent of the relative potency of the stimuli tested (Figure 12.10).

The observation that olive oil polyphenols decrease VCAM-1 protein expression regardless of the agonist suggests that olive oil polyphenols act downstream of membrane receptors, possibly through interference with ROS production and redox-sensitive transcription factor activation involved in VCAM-1 induction.44 Most relevant, such effects occurred at low micromolar concentrations within the plasma concentration range expected to be achieved with a classical Mediterranean diet.50 It is likely that such beneficial effects would be amplified in vivo because of the continuous exposure of vascular endothelia to these compounds.

LPS 1 ig/mL

+ Oleuropein, 15nmol/L Hydroxytyrosol, 15nmol/L

FIGURE 12.9 Olive oil polyphenols inhibit LPS-stimulated expression of various endothelial adhesion molecules. HUVEC were treated with polyphenols (15 mmol/L) for 30 min and then stimulated with LPS. Adhesion molecule expression was assessed by cell-surface EIA by specific monoclonal antibodies. All data are plotted as percentage of maximum control response (percent of stimulated response without polyphenols). Control vehicles (ethanol 0.05% vol/vol or methanol 0.005% vol/vol) had no effect on stimulated expression of VCAM-1. Data are based on six different experiments, each consisting of eight or more repeats for each condition. ** P < 0.01 vs. LPS alone.

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