title: Impact of Virgin Olive Oil and Phenol-Enriched Virgin Olive Oils on the HDL Proteome in Hypercholesterolemic Subjects: A Double Blind, Randomized, Controlled, Cross-Over Clinical Trial (VOHF Study).
abstract: The effects of olive oil phenolic compounds (PCs) on HDL proteome, with respect to new aspects of cardioprotective properties, are still unknown. The aim of this study was to assess the impact on the HDL protein cargo of the intake of virgin olive oil (VOO) and two functional VOOs, enriched with their own PCs (FVOO) or complemented with thyme PCs (FVOOT), in hypercholesterolemic subjects. Eligible volunteers were recruited from the IMIM-Hospital del Mar Medical Research Institute (Spain) from April 2012 to September 2012. Thirty-three hypercholesterolemic participants (total cholesterol >200 mg/dL; 19 men and 14 women; aged 35 to 80 years) were randomized in the double-blind, controlled, cross-over VOHF clinical trial. The subjects received for 3 weeks 25 mL/day of: VOO, FVOO, or FVOOT. Using a quantitative proteomics approach, 127 HDL-associated proteins were identified. Among these, 15 were commonly differently expressed after the three VOO interventions compared to baseline, with specific changes observed for each intervention. The 15 common proteins were mainly involved in the following pathways: LXR/RXR activation, acute phase response, and atherosclerosis. The three VOOs were well tolerated by all participants. Consumption of VOO, or phenol-enriched VOOs, has an impact on the HDL proteome in a cardioprotective mode by up-regulating proteins related to cholesterol homeostasis, protection against oxidation and blood coagulation while down-regulating proteins implicated in acute-phase response, lipid transport, and immune response. The common observed protein expression modifications after the three VOOs indicate a major matrix effect.
  
  
  BACKGROUND
  International Standard Randomized Controlled Trials ISRCTN77500181.
authors.affiliation: Research Unit on Lipids and Atherosclerosis, CTNS, CIBERDEM, Hospital Universitari Sant Joan, Servei de Medicina Interna, IISPV, Universitat Rovira i Virgili, Reus, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Pedret
authors.affiliation: Research Unit on Lipids and Atherosclerosis, CTNS, CIBERDEM, Hospital Universitari Sant Joan, Servei de Medicina Interna, IISPV, Universitat Rovira i Virgili, Reus, Spain.
authors.forename: Úrsula
authors.initials: Ú
authors.lastname: Catalán
authors.affiliation: Research Unit on Lipids and Atherosclerosis, CTNS, CIBERDEM, Hospital Universitari Sant Joan, Servei de Medicina Interna, IISPV, Universitat Rovira i Virgili, Reus, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Fernández-Castillejo
authors.affiliation: Cardiovascular Risk and Nutrition Research Group (CARIN, Regicor Study Group), CIBER de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain; Ph.D. Program in Biochemistry, Molecular Biology and Biomedicine, Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Farràs
authors.affiliation: Research Unit on Lipids and Atherosclerosis, CTNS, CIBERDEM, Hospital Universitari Sant Joan, Servei de Medicina Interna, IISPV, Universitat Rovira i Virgili, Reus, Spain.
authors.forename: Rosa-M
authors.initials: RM
authors.lastname: Valls
authors.affiliation: Food Technology Department, UTPV-XaRTA, University of Lleida-AGROTECNIO Research Centre, Lleida, Spain; Research Unit on Lipids and Atherosclerosis, CTNS, CIBERDEM, Hospital Universitari Sant Joan, Servei de Medicina Interna, IISPV, Universitat Rovira i Virgili, Reus, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Rubió
authors.affiliation: Centre for Omic Sciences (COS), Universitat Rovira i Virgili, Reus, Spain.
authors.forename: Núria
authors.initials: N
authors.lastname: Canela
authors.affiliation: Centre for Omic Sciences (COS), Universitat Rovira i Virgili, Reus, Spain.
authors.forename: Gerard
authors.initials: G
authors.lastname: Aragonés
authors.affiliation: Pharmacology Unit, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Reus, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Romeu
authors.affiliation: Cardiovascular Risk and Nutrition Research Group (CARIN, Regicor Study Group), CIBER de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: Castañer
authors.affiliation: Human Pharmacology and Clinical Neurosciences Research Group, CIBER de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain; Universitat Pompeu Fabra (CEXS-UPF), Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: de la Torre
authors.affiliation: Cardiovascular Risk and Nutrition Research Group (CARIN, Regicor Study Group), CIBER de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Maria-Isabel
authors.initials: MI
authors.lastname: Covas
authors.affiliation: Cardiovascular Risk and Nutrition Research Group (CARIN, Regicor Study Group), CIBER de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Montse
authors.initials: M
authors.lastname: Fitó
authors.affiliation: Food Technology Department, UTPV-XaRTA, University of Lleida-AGROTECNIO Research Centre, Lleida, Spain.
authors.forename: Maria-José
authors.initials: MJ
authors.lastname: Motilva
authors.affiliation: Research Unit on Lipids and Atherosclerosis, CTNS, CIBERDEM, Hospital Universitari Sant Joan, Servei de Medicina Interna, IISPV, Universitat Rovira i Virgili, Reus, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Solà
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D008076:Cholesterol, HDL / Q000097:blood*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D000069463:Olive Oil / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D010636:Phenols / Q000008:administration & dosage / Q000494:pharmacology; D020543:Proteome / Q000032:analysis* / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D008076:Cholesterol, HDL; D000069463:Olive Oil; D010636:Phenols; D020543:Proteome