Mediterranean Diet Modulates Gene Expression of Cholesterol Efflux Receptors in High‐Risk Cardiovascular Patients

In this study, we investigated gene expression related to cholesterol efflux receptors in individuals at high cardiovascular risk undergoing Mediterranean dietary interventions. Through transcriptomic analysis, we examined samples from two randomized controlled trials: PREDIMED and PREDIMED-Plus, with 151 and 89 elderly adults, respectively. Blood cells were isolated at baseline and after a 12-month intervention. In the PREDIMED trial, participants followed different Mediterranean diets: one supplemented with extra-virgin olive oil (traditional Mediterranean diet enriched with extra-virgin olive oil [MedDiet-EVOO]), another with nuts (MedDiet enriched with nuts MedDiet-Nuts [MedDiet-Nuts]), and a low-fat control diet. The PREDIMED-Plus trial compared an energy-reduced Mediterranean diet (Er-MedDiet) with physical activity to an ad libitum Mediterranean diet. Over time, mild but significant upregulation of genes like ATP binding cassette subfamily A member 1 (ABCA1), retinoid X receptor alpha (RXRA), retinoid X receptor beta (RXRB), and Nuclear Receptor Subfamily 1 Group H Member 3 (NR1H3) was observed in response to MedDiet-EVOO, MedDiet-Nuts, and Er-MedDiet. Notably, RXRA expression was higher in both MedDiet-EVOO and MedDiet-Nuts compared to the control diet. Differences in gene expression, particularly RXRA, ATP binding cassette subfamily G member 1 (ABCG1), NR1H3, and Peroxisome Proliferator Activated Receptor Delta (PPARD), were evident between MedDiet-Nuts and the control diet. In the PREDIMED-Plus trial, no significant differences in gene expression were found between dietary groups. Principal component analysis (PCA) and linear discriminant analysis (LDA) showed overlapping gene expression profiles across different Mediterranean diet interventions. In conclusion, our study highlights the cardiovascular health benefits of long-term adherence to a Mediterranean diet, both normocaloric and hypocaloric, primarily reflected by mild upregulation of cholesterol efflux-related genes-specifically involving RXRA, RXRB, ABCA1, ABCG1, Nuclear Receptor Subfamily 1 Group H Member 2(NR1H2), and PPARD-among elderly adults at high cardiovascular risk. This suggests a potential mechanism by which these diets may exert cardiovascular protective effects.

Authors

Institutions

Publication Details

Journal
Molecular Nutrition & Food Research
Published
2025-05-09
DOI
https://doi.org/10.1002/mnfr.70050
Citations
6
Primary Topic
Cholesterol and Lipid Metabolism
Type
article
Field-Weighted Citation Impact
12.04

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Mediterranean Diet Modulates Gene Expression of Cholesterol Efflux Receptors in High‐Risk Cardiovascular Patients

Mireia Malcampo, Fernando Arós, Jordi Salas‐Salvadó, Montserrat Fitó et al.
6 citations
Molecular Nutrition & Food Research
Cholesterol and Lipid Metabolism
12.04
article

Mediterranean Diet Modulates Gene Expression of Cholesterol Efflux Receptors in High‐Risk Cardiovascular Patients

Mireia Malcampo, Fernando Arós, Jordi Salas‐Salvadó, Montserrat Fitó, Dolores Corella, Xavier Pintó, Daniel Muñoz‐Aguayo, José Lapetra, Rosa Maria Lamuela-Raventós, Enrique Gómez‐Gracia, Miguel Ángel Martínez‐González, Dora Romaguera, Álvaro Hernáez, Francisco José Tinahones, Emilio Ros, Albert Sanllorente, Javier Hernando‐Redondo, Lluís Serra‐Majem, Olga Castañer, Isaac Subirana, Ramón Estruch
article en
6 citations

Abstract

In this study, we investigated gene expression related to cholesterol efflux receptors in individuals at high cardiovascular risk undergoing Mediterranean dietary interventions. Through transcriptomic analysis, we examined samples from two randomized controlled trials: PREDIMED and PREDIMED-Plus, with 151 and 89 elderly adults, respectively. Blood cells were isolated at baseline and after a 12-month intervention. In the PREDIMED trial, participants followed different Mediterranean diets: one supplemented with extra-virgin olive oil (traditional Mediterranean diet enriched with extra-virgin olive oil [MedDiet-EVOO]), another with nuts (MedDiet enriched with nuts MedDiet-Nuts [MedDiet-Nuts]), and a low-fat control diet. The PREDIMED-Plus trial compared an energy-reduced Mediterranean diet (Er-MedDiet) with physical activity to an ad libitum Mediterranean diet. Over time, mild but significant upregulation of genes like ATP binding cassette subfamily A member 1 (ABCA1), retinoid X receptor alpha (RXRA), retinoid X receptor beta (RXRB), and Nuclear Receptor Subfamily 1 Group H Member 3 (NR1H3) was observed in response to MedDiet-EVOO, MedDiet-Nuts, and Er-MedDiet. Notably, RXRA expression was higher in both MedDiet-EVOO and MedDiet-Nuts compared to the control diet. Differences in gene expression, particularly RXRA, ATP binding cassette subfamily G member 1 (ABCG1), NR1H3, and Peroxisome Proliferator Activated Receptor Delta (PPARD), were evident between MedDiet-Nuts and the control diet. In the PREDIMED-Plus trial, no significant differences in gene expression were found between dietary groups. Principal component analysis (PCA) and linear discriminant analysis (LDA) showed overlapping gene expression profiles across different Mediterranean diet interventions. In conclusion, our study highlights the cardiovascular health benefits of long-term adherence to a Mediterranean diet, both normocaloric and hypocaloric, primarily reflected by mild upregulation of cholesterol efflux-related genes-specifically involving RXRA, RXRB, ABCA1, ABCG1, Nuclear Receptor Subfamily 1 Group H Member 2(NR1H2), and PPARD-among elderly adults at high cardiovascular risk. This suggests a potential mechanism by which these diets may exert cardiovascular protective effects.

Molecular Nutrition & Food ResearchVol. 69(13)
Universidad de Las Palmas de Gran Canaria (ES), Universitat de València (ES), University of the Basque Country (ES), Instituto de Salud Carlos III (ES), Institut d'Investigació Biomédica de Bellvitge (ES), Centro de Investigación en Red en Enfermedades Cardiovasculares (ES), Institut de Recerca Biomèdica Catalunya Sud (ES), Hospital Universitario Araba (ES), Navarre Institute of Health Research (ES), Health Research Institute of the Balearic Islands (ES), Institut Universitari d'Investigació en Atenció Primària Jordi Gol (ES), Hospital Del Mar (ES), Institut Català de la Salut (ES), Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (ES), Hospital del Mar Research Institute (ES), Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES), Instituto de Investigación Biomédica de Málaga (ES), Universitat Ramon Llull (ES), Universitat Rovira i Virgili (ES), Universitat de Barcelona (ES), Universidad de Málaga (ES), Universidad de Navarra (ES)
Fundació la Marató de TV3, European Commission, Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición, Agència de Gestió d'Ajuts Universitaris i de Recerca, Instituto de Salud Carlos III, European Social Fund
Openalex Percentile: Top 1%
Cholesterol and Lipid Metabolism
12.04
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.