title: Extra virgin olive oil rich in polyphenols modulates VEGF-induced angiogenic responses by preventing NADPH oxidase activity and expression.
abstract: Previous studies have shown the antiinflammatory, antioxidant and antiangiogenic properties by pure olive oil polyphenols; however, the effects of olive oil phenolic fraction on the inflammatory angiogenesis are unknown. In this study, we investigated the effects of the phenolic fraction (olive oil polyphenolic extract, OOPE) from extra virgin olive oil and related circulating metabolites on the VEGF-induced angiogenic responses and NADPH oxidase activity and expression in human cultured endothelial cells. We found that OOPE (1-10 μg/ml), at concentrations achievable nutritionally, significantly reduced, in a concentration-dependent manner, the VEGF-induced cell migration, invasiveness and tube-like structure formation through the inhibition of MMP-2 and MMP-9. OOPE significantly (P<0.05) reduced VEGF-induced intracellular reactive oxygen species by modulating NADPH oxidase activity, p47phox membrane translocation and the expression of Nox2 and Nox4. Moreover, the treatment of endothelial cells with serum obtained 4 h after acute intake of extra virgin olive oil, with high polyphenol content, decreased VEGF-induced NADPH oxidase activity and Nox4 expression, as well as, MMP-9 expression, as compared with fasting control serum. Overall, native polyphenols and serum metabolites of extra virgin olive oil rich in polyphenols are able to lower the VEGF-induced angiogenic responses by preventing endothelial NADPH oxidase activity and decreasing the expression of selective NADPH oxidase subunits. Our results provide an alternative mechanism by which the consumption of olive oil rich in polyphenols may account for a reduction of oxidative stress inflammatory-related sequelae associated with chronic degenerative diseases.
authors.affiliation: National Research Council - Institute of Clinical Physiology, Lecce, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Calabriso
authors.affiliation: National Research Council - Institute of Clinical Physiology, Lecce, Italy.
authors.forename: Marika
authors.initials: M
authors.lastname: Massaro
authors.affiliation: National Research Council - Institute of Clinical Physiology, Lecce, Italy.
authors.forename: Egeria
authors.initials: E
authors.lastname: Scoditti
authors.affiliation: Clinica Medica "A. Murri", University of Bari Medical School, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: D'Amore
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Gnoni
authors.affiliation: National Research Council - Institute of Clinical Physiology, Lecce, Italy; Department of Biological and Environmental Science and Technologies, University of Lecce, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Pellegrino
authors.affiliation: Department of Biological and Environmental Science and Technologies, University of Lecce, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Storelli
authors.affiliation: "G. Monasterio" Foundation for Clinical Research, Pisa, Italy; "G. d'Annunzio" University and Center of Excellence on Aging, Chieti, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Caterina
authors.affiliation: Clinica Medica "A. Murri", University of Bari Medical School, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palasciano
authors.affiliation: National Research Council - Institute of Clinical Physiology, Lecce, Italy. Electronic address: maria.carluccio@ifc.cnr.it.
authors.forename: Maria Annunziata
authors.initials: MA
authors.lastname: Carluccio
mesh_terms: D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors*; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D000069463:Olive Oil / Q000737:chemistry*; D059808:Polyphenols / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*
chemical_list: D000069463:Olive Oil; D059808:Polyphenols; D042461:Vascular Endothelial Growth Factor A; D019255:NADPH Oxidases
keywords: Endothelial cells; Matrix metalloproteinases; Nox2; Nox4; Oxidative stress; p47phox