title: Effects of polyphenol extract from olive pomace on anoxia-induced endothelial dysfunction.
abstract: Anoxia modulates the expression of molecules associated with endothelial dysfunction and vascular diseases. Polyphenols have potent antioxidant properties due to their ability to modulate genes involved in oxidative tissue damage. In this study, we investigated the effect of polyphenol extract from olive pomace (PEOP) and its main constituents, Tyrosol and Oleuropein, on endothelial cells subjected to anoxia by evaluating the expression of molecules critical for endothelial function, proliferation and migration, and the signaling pathway involved. EAhy926 human endothelial cells were exposed to anoxic stress in the presence or absence of PEOP. Anoxia increased the nitric oxide (NO) level and the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNFα). These effects were prevented by PEOP treatment in a dose-dependent manner. Moreover, PEOP prevented the proliferation and migration associated with anoxia in EAhy926 cells, down-regulated the levels of matrix metalloproteinase (MMP)-2, MMP-9 and membrane type-1 MMP (MT1-MMP) and increased tissue MMP inhibitor-1 (TIMP-1) expression. Purified Oleuropein or Tyrosol restored to a basal level the anoxia-induced expression of MMP-9 and partially of MMP-2. The expression of TNFα was reduced by both polyphenols in a dose-dependent manner, but more efficiently by Tyrosol. Conversely, Oleuropein and Tyrosol had no significant effects on iNOS, COX-2 and TIMP-1 expression when used at the concentration found in PEOP. PEOP induced a time-dependent phosphorylation of p38 MAPK and ERK1/2 and inhibited anoxia-induced NF-κB activation. PEOP treatment restores the endothelial functions that are impaired by anoxia by regulating the expression of genes involved in proteolysis, angiogenesis and inflammation more efficiently than the single purified components. Therefore, the combined use of polyphenols, as in PEOP, could represent a powerful tool for the treatment and chemoprevention of endothelial dysfunction-associated vascular diseases.
authors.affiliation: Vascular and Endovascular Surgery Unit, Research Laboratory of Experimental and Clinical Vascular Biology, DISC, University of Genoa and IRCCS San Martino Hospital, Largo Rosanna Benzi, 16132 Genoa, Italy. danielapalmieri@yahoo.com
authors.forename: Daniela
authors.initials: D
authors.lastname: Palmieri
authors.forename: Bahar
authors.initials: B
authors.lastname: Aliakbarian
authors.forename: Alessandro Alberto
authors.initials: AA
authors.lastname: Casazza
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Ferrari
authors.forename: Giovanni
authors.initials: G
authors.lastname: Spinella
authors.forename: Bianca
authors.initials: B
authors.lastname: Pane
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cafueri
authors.forename: Patrizia
authors.initials: P
authors.lastname: Perego
authors.forename: Domenico
authors.initials: D
authors.lastname: Palombo
mesh_terms: D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000473:pathology*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D053511:Matrix Metalloproteinase 14 / Q000096:biosynthesis; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D031658:Olea / Q000378:metabolism*; D010766:Phosphorylation; D059808:Polyphenols / Q000737:chemistry*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D059808:Polyphenols; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D053511:Matrix Metalloproteinase 14