title: Protective effect of hydroxytyrosol and its predominant plasmatic human metabolites against endothelial dysfunction in human aortic endothelial cells.
abstract: METHODS
  Hydroxytyrosol (HT) is the major phenolic compound in virgin olive oil (VOO) in free and conjugated forms that may exert health benefits against atherosclerosis. The native form of HT is undetectable in plasma due to an extensive first pass phase II metabolism. Therefore, it is necessary to find strategies to obtain HT metabolites and to demonstrate their protective role against the endothelial dysfunction.
  
  
  RESULTS
  Biosynthesis of the main plasmatic HT metabolites was performed through Caco-2 cells. The bioactivity of HT and the mixture of metabolites was tested at physiological concentrations (1, 2, 5, and 10 μM) in human aortic endothelial cells (HAEC) co-incubated with TNF-α (10 ng/mL) for 18 and 24 h. After the incubations, cells and media were analyzed to test possible deconjugation of metabolites or conjugation of HT. Both HT and metabolites significantly reduced the secretion of E-selectin, P-selectin, ICAM-1, and VCAM-1, but only HT metabolites further reduced MCP-1 at 24 h. HT underwent a conjugation process after incubation leading to its main metabolites in a dose-dependent manner.
  
  
  CONCLUSIONS
  Physiological HT metabolites, synthetized for the first time by using an intestinal cell model, might be responsible in part for the protection against endothelial dysfunction.
authors.affiliation: Functional Nutrition, Oxidation and Cardiovascular Diseases Group (NFOC-Salut), Unit of Lipids and Atherosclerosis Research (URLA), Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Hospital Universitari Sant Joan, IISPV, Technological Center of Nutrition and Health (CTNS), Faculty of Medicine and Health Sciences, Universitat Rovira i Virgili, Reus, Spain.
authors.forename: Úrsula
authors.initials: Ú
authors.lastname: Catalán
authors.affiliation: Food Technology Department, Universitat de Lleida-AGROTECNIO Center, Lleida, Lleida, Spain.
authors.forename: Maria-Carmen
authors.initials: MC
authors.lastname: López de Las Hazas
authors.affiliation: Functional Nutrition, Oxidation and Cardiovascular Diseases Group (NFOC-Salut), Unit of Lipids and Atherosclerosis Research (URLA), Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Hospital Universitari Sant Joan, IISPV, Technological Center of Nutrition and Health (CTNS), Faculty of Medicine and Health Sciences, Universitat Rovira i Virgili, Reus, Spain.|Food Technology Department, Universitat de Lleida-AGROTECNIO Center, Lleida, Lleida, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Rubió
authors.affiliation: Functional Nutrition, Oxidation and Cardiovascular Diseases Group (NFOC-Salut), Unit of Lipids and Atherosclerosis Research (URLA), Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Hospital Universitari Sant Joan, IISPV, Technological Center of Nutrition and Health (CTNS), Faculty of Medicine and Health Sciences, Universitat Rovira i Virgili, Reus, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Fernández-Castillejo
authors.affiliation: Functional Nutrition, Oxidation and Cardiovascular Diseases Group (NFOC-Salut), Unit of Lipids and Atherosclerosis Research (URLA), Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Hospital Universitari Sant Joan, IISPV, Technological Center of Nutrition and Health (CTNS), Faculty of Medicine and Health Sciences, Universitat Rovira i Virgili, Reus, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Pedret
authors.affiliation: Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Facultat de Ciencies de la Salut i de la Vida, Universitat Pompeu Fabra (CEXS-UPF), Institut Hospital del Mar d'Investigacions Mediques (IMIM), Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: de la Torre
authors.affiliation: Food Technology Department, Universitat de Lleida-AGROTECNIO Center, Lleida, Lleida, Spain.
authors.forename: Maria-José
authors.initials: MJ
authors.lastname: Motilva
authors.affiliation: Functional Nutrition, Oxidation and Cardiovascular Diseases Group (NFOC-Salut), Unit of Lipids and Atherosclerosis Research (URLA), Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Hospital Universitari Sant Joan, IISPV, Technological Center of Nutrition and Health (CTNS), Faculty of Medicine and Health Sciences, Universitat Rovira i Virgili, Reus, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Solà
mesh_terms: D001011:Aorta / Q000166:cytology / Q000187:drug effects; D018938:Caco-2 Cells; D018932:Chemokine CCL2 / Q000378:metabolism; D003470:Culture Media; D019040:E-Selectin / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D020011:Protective Agents / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D003470:Culture Media; D019040:E-Selectin; D019007:P-Selectin; D020011:Protective Agents; C546936:SELE protein, human; D019010:Vascular Cell Adhesion Molecule-1; C005975:3,4-dihydroxyphenylethanol; D018799:Intercellular Adhesion Molecule-1; D010626:Phenylethyl Alcohol
keywords: Atherosclerosis; Caco-2; Human aortic endothelial cells; Hydroxytyrosol; Hydroxytyrosol metabolites