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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).

Pedret A, Catalán Ú, Fernández-Castillejo S, Farràs M, Valls RM, Rubió L, Canela N, Aragonés G, Romeu M, Castañer O, de la Torre R, Covas MI, Fitó M, Motilva MJ, Solà R - PLoS ONE (2015)

Bottom Line: The effects of olive oil phenolic compounds (PCs) on HDL proteome, with respect to new aspects of cardioprotective properties, are still unknown.The three VOOs were well tolerated by all participants.The common observed protein expression modifications after the three VOOs indicate a major matrix effect.

View Article: PubMed Central - PubMed

Affiliation: Research Unit on Lipids and Atherosclerosis, CTNS, CIBERDEM, Hospital Universitari Sant Joan, Servei de Medicina Interna, IISPV, Universitat Rovira i Virgili, Reus, Spain.

ABSTRACT

Unlabelled: 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.

Trial registration: International Standard Randomized Controlled Trials ISRCTN77500181.

No MeSH data available.


Related in: MedlinePlus

Venn diagram showing intersections of proteins differentially expressed after VOO, FVOO, and FVOOT interventions.Proteins are presented with their gene encode symbol. Red proteins: up-regulated; green proteins: down-regulated. VOO: Virgin Olive Oil; FVOO: Functional Virgin Olive Oil enriched with its own PCs; FVOOT: Functional Virgin Olive Oil enriched with its own PCs plus complementary phenols from thyme.
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pone.0129160.g004: Venn diagram showing intersections of proteins differentially expressed after VOO, FVOO, and FVOOT interventions.Proteins are presented with their gene encode symbol. Red proteins: up-regulated; green proteins: down-regulated. VOO: Virgin Olive Oil; FVOO: Functional Virgin Olive Oil enriched with its own PCs; FVOOT: Functional Virgin Olive Oil enriched with its own PCs plus complementary phenols from thyme.

Mentions: Compared to baseline values (first visit), the HDL protein cargoes of the differentially expressed proteins differed after the interventions according to the VOO received. The complete list of the proteins differentially expressed after each VOO intervention, and their principal biological functions, are shown in S5 Table. The proteins were associated with a broad range of biological functions, principally cholesterol homeostasis, lipid transport, acute-phase response, blood coagulation, immune response, protection against oxidation, and proteolysis. The proteins differently modulated after VOO, FVOO, and FVOOT interventions and associated with these main functions are represented in Fig 4. The overlapping among interventions indicates that 15 proteins were commonly up- or down-regulated after the three VOO interventions. These proteins were: Serum paraxonase/lactonase 3 (PON3), Apo A-II, Apo A-I, Apo D, Retinol binding protein 4 (RBP4), Heparin cofactor 2 (SERPIND1), zinc-alpha-2-glycoprotein (AZGP1), alpha-2-antiplasmin (SERPINF2), alpha-2-HS-glycoprotein (AHSG), clusterin (CLU), alpha-2-macroglobulin (A2M), haptoglobin (HP), alpha-1-acid glycoprotein (ORM1), Beta-Ala-His dipeptidase (CNDP1), and Aminopeptidase N (ANPEP). These 15 proteins that were observed to have the greatest expression modifications were identified with both MS techniques, nano LC-MALDI MS/MS and nano LC-ORBITRAP-ESI MS/MS. A protein-protein interaction network was generated for the 15 common, differentially expressed proteins using database and web-tool STRING 9.1 (S1 Fig). The common up-regulated proteins were related to cholesterol homeostasis, blood coagulation and protection against oxidation; the common down-regulated proteins were implicated in acute-phase response, lipid transport, immune response, and proteolysis. All proteins except for ANPEP and CNDP1, which are involved in proteolysis, appeared in the center of the functional network intersection indicating their key role in protein interactions. The information of these relevant proteins commonly regulated by the three VOO interventions was summarized in Table 2.


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).

Pedret A, Catalán Ú, Fernández-Castillejo S, Farràs M, Valls RM, Rubió L, Canela N, Aragonés G, Romeu M, Castañer O, de la Torre R, Covas MI, Fitó M, Motilva MJ, Solà R - PLoS ONE (2015)

Venn diagram showing intersections of proteins differentially expressed after VOO, FVOO, and FVOOT interventions.Proteins are presented with their gene encode symbol. Red proteins: up-regulated; green proteins: down-regulated. VOO: Virgin Olive Oil; FVOO: Functional Virgin Olive Oil enriched with its own PCs; FVOOT: Functional Virgin Olive Oil enriched with its own PCs plus complementary phenols from thyme.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4465699&req=5

pone.0129160.g004: Venn diagram showing intersections of proteins differentially expressed after VOO, FVOO, and FVOOT interventions.Proteins are presented with their gene encode symbol. Red proteins: up-regulated; green proteins: down-regulated. VOO: Virgin Olive Oil; FVOO: Functional Virgin Olive Oil enriched with its own PCs; FVOOT: Functional Virgin Olive Oil enriched with its own PCs plus complementary phenols from thyme.
Mentions: Compared to baseline values (first visit), the HDL protein cargoes of the differentially expressed proteins differed after the interventions according to the VOO received. The complete list of the proteins differentially expressed after each VOO intervention, and their principal biological functions, are shown in S5 Table. The proteins were associated with a broad range of biological functions, principally cholesterol homeostasis, lipid transport, acute-phase response, blood coagulation, immune response, protection against oxidation, and proteolysis. The proteins differently modulated after VOO, FVOO, and FVOOT interventions and associated with these main functions are represented in Fig 4. The overlapping among interventions indicates that 15 proteins were commonly up- or down-regulated after the three VOO interventions. These proteins were: Serum paraxonase/lactonase 3 (PON3), Apo A-II, Apo A-I, Apo D, Retinol binding protein 4 (RBP4), Heparin cofactor 2 (SERPIND1), zinc-alpha-2-glycoprotein (AZGP1), alpha-2-antiplasmin (SERPINF2), alpha-2-HS-glycoprotein (AHSG), clusterin (CLU), alpha-2-macroglobulin (A2M), haptoglobin (HP), alpha-1-acid glycoprotein (ORM1), Beta-Ala-His dipeptidase (CNDP1), and Aminopeptidase N (ANPEP). These 15 proteins that were observed to have the greatest expression modifications were identified with both MS techniques, nano LC-MALDI MS/MS and nano LC-ORBITRAP-ESI MS/MS. A protein-protein interaction network was generated for the 15 common, differentially expressed proteins using database and web-tool STRING 9.1 (S1 Fig). The common up-regulated proteins were related to cholesterol homeostasis, blood coagulation and protection against oxidation; the common down-regulated proteins were implicated in acute-phase response, lipid transport, immune response, and proteolysis. All proteins except for ANPEP and CNDP1, which are involved in proteolysis, appeared in the center of the functional network intersection indicating their key role in protein interactions. The information of these relevant proteins commonly regulated by the three VOO interventions was summarized in Table 2.

Bottom Line: The effects of olive oil phenolic compounds (PCs) on HDL proteome, with respect to new aspects of cardioprotective properties, are still unknown.The three VOOs were well tolerated by all participants.The common observed protein expression modifications after the three VOOs indicate a major matrix effect.

View Article: PubMed Central - PubMed

Affiliation: Research Unit on Lipids and Atherosclerosis, CTNS, CIBERDEM, Hospital Universitari Sant Joan, Servei de Medicina Interna, IISPV, Universitat Rovira i Virgili, Reus, Spain.

ABSTRACT

Unlabelled: 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.

Trial registration: International Standard Randomized Controlled Trials ISRCTN77500181.

No MeSH data available.


Related in: MedlinePlus