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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

Top scored associated network generated by IPA describing common differentially expressed proteins after all VOO interventions.The top scoring significantly associated network was assessed with Fisher’s exact test (p<0.01). Proteins were presented with their gene encode symbol. The proteins indicated in red and green are those whose expression levels were significantly up- or down-regulated, respectively. Proteins indicated in white are those available in the IPA database, but not detected as differentially expressed in the present study. The shapes of the symbols denote the molecular class of proteins. Solid lines indicate direct molecular interactions, whereas dashed lines indicate indirect molecular interactions.
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pone.0129160.g007: Top scored associated network generated by IPA describing common differentially expressed proteins after all VOO interventions.The top scoring significantly associated network was assessed with Fisher’s exact test (p<0.01). Proteins were presented with their gene encode symbol. The proteins indicated in red and green are those whose expression levels were significantly up- or down-regulated, respectively. Proteins indicated in white are those available in the IPA database, but not detected as differentially expressed in the present study. The shapes of the symbols denote the molecular class of proteins. Solid lines indicate direct molecular interactions, whereas dashed lines indicate indirect molecular interactions.

Mentions: IPA analysis was performed to reveal the canonical pathways significantly affected (p<0.01) by OO phenols. The top 7 signaling pathways modified by the differentially expressed common proteins after all VOO interventions included: LXR/RXR activation, acute phase response signaling, atherosclerosis signaling, IL-12 signaling and production in macrophages, production of nitric oxide (NO) and reactive oxygen species (ROS) in macrophages, Clathrin-mediated endocytosis signaling, and coagulation system (Fig 6). Our results showed that OO phenols tended to have a strong effect on LXR/RXR activation (p = 2.39E-16; ratio = 0.071), followed by acute phase response signaling (p = 4.91E-15; ratio = 0.052). The highest scoring associated network generated by IPA, and the differentially expressed proteins common for all VOO interventions, are shown in Fig 7. The top scoring significantly associated network (score = 30) included 12 focused proteins and several associated genes, and was related to the following biological functions: lipid metabolism, small molecule biochemistry, and molecular transport. The nuclear receptor subfamily 5, group A, member 2 (NR5A2) and interleukin 6 (IL-6) were associated genes appearing in this network and representing the significantly affected top upstream regulators (p<0.01). NR5A2, which is implicated in the canonical pathway of FXR/RXR activation and the biological process of cholesterol homeostasis, was predicted from our results to be activated. Likewise, IL-6, which is involved in the acute phase response canonical pathway, was expected to be inhibited.


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)

Top scored associated network generated by IPA describing common differentially expressed proteins after all VOO interventions.The top scoring significantly associated network was assessed with Fisher’s exact test (p<0.01). Proteins were presented with their gene encode symbol. The proteins indicated in red and green are those whose expression levels were significantly up- or down-regulated, respectively. Proteins indicated in white are those available in the IPA database, but not detected as differentially expressed in the present study. The shapes of the symbols denote the molecular class of proteins. Solid lines indicate direct molecular interactions, whereas dashed lines indicate indirect molecular interactions.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0129160.g007: Top scored associated network generated by IPA describing common differentially expressed proteins after all VOO interventions.The top scoring significantly associated network was assessed with Fisher’s exact test (p<0.01). Proteins were presented with their gene encode symbol. The proteins indicated in red and green are those whose expression levels were significantly up- or down-regulated, respectively. Proteins indicated in white are those available in the IPA database, but not detected as differentially expressed in the present study. The shapes of the symbols denote the molecular class of proteins. Solid lines indicate direct molecular interactions, whereas dashed lines indicate indirect molecular interactions.
Mentions: IPA analysis was performed to reveal the canonical pathways significantly affected (p<0.01) by OO phenols. The top 7 signaling pathways modified by the differentially expressed common proteins after all VOO interventions included: LXR/RXR activation, acute phase response signaling, atherosclerosis signaling, IL-12 signaling and production in macrophages, production of nitric oxide (NO) and reactive oxygen species (ROS) in macrophages, Clathrin-mediated endocytosis signaling, and coagulation system (Fig 6). Our results showed that OO phenols tended to have a strong effect on LXR/RXR activation (p = 2.39E-16; ratio = 0.071), followed by acute phase response signaling (p = 4.91E-15; ratio = 0.052). The highest scoring associated network generated by IPA, and the differentially expressed proteins common for all VOO interventions, are shown in Fig 7. The top scoring significantly associated network (score = 30) included 12 focused proteins and several associated genes, and was related to the following biological functions: lipid metabolism, small molecule biochemistry, and molecular transport. The nuclear receptor subfamily 5, group A, member 2 (NR5A2) and interleukin 6 (IL-6) were associated genes appearing in this network and representing the significantly affected top upstream regulators (p<0.01). NR5A2, which is implicated in the canonical pathway of FXR/RXR activation and the biological process of cholesterol homeostasis, was predicted from our results to be activated. Likewise, IL-6, which is involved in the acute phase response canonical pathway, was expected to be inhibited.

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