Entry #: 28
Date: 12 December 2017
Section: Vascular biology
Topic: Mediterranean polyphenols and endothelial cells
Type: Original article
OliveNetTM Journal Club
Expert review of literature related to olives and olive oil
D. Elizabeth McCord, Nancy B. Ray and Tom C. Karagiannis
Mediterranean diet polyphenols reduce inflammatory angiogenesis through MMP-9 and COX-2 inhibition in human vascular endothelial cells: A potentially protective mechanism in atherosclerotic vascular disease and cancer
Scoditti et al
Citation / Year
(1) / 2012
Oleuropein, hydroxytyrosol, resveratrol, quercetin, vascular endothelial cells, angiogenesis, matrix metalloproteinase, cyclooxygenase
The Mediterranean diet has been associated with a decrease of numerous diseases which are linked to inflammation and oxidative stress including cardiovascular and metabolic diseases, neurodegeneration and cancer (2-8). The current paradigm indicates that the high antioxidant polyphenols which form part of the Mediterranean diet are largely responsible for the beneficial for the health effects (9-12). Major phenolics from virgin olive oil (including oleuropein and hydroxytyrosol) (13, 14), and from red wine (resveratrol and quercetin) (15-18), have been shown to possess potent antioxidant and anti-inflammatory effects. In this study, the effects of these major dietary polyphenols on endothelial cell inflammation and angiogenesis was investigated. In particular, the regulation of oleuropein, hydroxytyrosol, resveratrol and quercetin on the regulation of the key inflammatory response associated cyclooxygenase-2 enzyme (COX-2) and matrix metalloproteinase-9 (MMP-9) linked to angiogenesis was investigated.
Key points and implications
Human umbilical vein endothelial cells (and human microvascular endothelial-1 cells, for selected control experiments), were used in this study. Cells were stimulated with phorbol 12-myristate 13-acetate (PMA) and treated with or without 0.1-50 μM polyphenols. Conventional matrigel tube formation and scratch migration assays were performed and to elucidate molecular mechanisms of action, immunoblotting and immunocytochemistry experiments were conducted. Firstly, it is important to note that treatment of cells with up to 50 μM of the polyphenols for 24 hours did not produce any signs of cytotoxicity. The key findings indicated that oleuropein, hydroxytyrosol, resveratrol and quercetin: 1) inhibit angiogenic responses in PMA-stimulated endothelial cells as assessed by scratch migration and tube formation experiments, 2) inhibit MMP-9 activity and expression in PMA-stimulated endothelial cells, 3) inhibit PMA-induced COX-2 activity and expression, and 4) reduce PMA-mediated levels of reactive oxygen species and nuclear factor (NF)-B. In summary these findings highlight that the dietary polyphenols produce anti-inflammatory and anti-angiogenic effects in stimulated endothelial cells via the reactive oxygen species-mediated NF-B pathway resulting in the modulation of the expression of MMP-9 and COX-2. In general, these basic in vitro studies are important for delineating the molecular mechanisms of action accounting the beneficial health effects of polyphenol-rich diets such as the Mediterranean diet.
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