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Anabel García-Heredia


ghanabel@gmail.com
Unitat de Recerca Biomèdica (URB-CRB)
Hospital Universitari de Sant Joan
Institut d'Investigació Sanitària Pere Virgili (IISPV)
Universitat Rovira i Virgili
C/ Sant Joan s/n
43201 Reus
SPAIN

Journal articles

2013
Anabel García-Heredia, Judit Marsillach, Anna Rull, Iris Triguero, Isabel Fort, Bharti Mackness, Michael Mackness, Diana M Shih, Jorge Joven, Jordi Camps (2013)  Paraoxonase-1 inhibits oxidized low-density lipoprotein-induced metabolic alterations and apoptosis in endothelial cells: a nondirected metabolomic study.   Mediators of inflammation 2013: 05  
Abstract: We studied the influence of PON1 on metabolic alterations induced by oxidized LDL when incubated with endothelial cells. HUVEC cells were incubated with native LDL, oxidized LDL, oxidized LDL plus HDL from wild type mice, and oxidized LDL plus HDL from PON1-deficient mice. Results showed alterations in carbohydrate and phospholipid metabolism and increased apoptosis in cells incubated with oxidized LDL. These changes were partially prevented by wild type mouse HDL, but the effects were less effective with HDL from PON1-deficient mice. Our results suggest that PON1 may play a significant role in endothelial cell survival by protecting cells from alterations in the respiratory chain induced by oxidized LDL. These results extend current knowledge on the protective role of HDL and PON1 against oxidation and apoptosis in endothelial cells.
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Anabel García-Heredia, Elizabeth Kensicki, Robert P Mohney, Anna Rull, Iris Triguero, Judit Marsillach, Carmen Tormos, Bharti Mackness, Michael Mackness, Diana M Shih, Juan Pedro-Botet, Jorge Joven, Guillermo Sáez, Jordi Camps (2013)  Paraoxonase-1 deficiency is associated with severe liver steatosis in mice fed a high-fat high-cholesterol diet. A metabolomic approach.   J Proteome Res Feb  
Abstract: Oxidative stress is a determinant of liver steatosis and the progression to more severe forms of disease. The present study investigated the effect of paraoxonase-1 (PON1) deficiency on histological alterations and hepatic metabolism in mice fed a high-fat high-cholesterol diet. We performed non-targeted metabolomics on liver tissues from 8 male PON1-deficient mice and 8 wild-type animals fed a high-fat, high-cholesterol diet for 22 weeks. We also measured 8-oxo-20-deoxyguanosine, reduced and oxidized glutathione, malondialdehyde, 8-isoprostanes and protein carbonyl concentrations. Results indicated lipid droplets in 14.5% of the hepatocytes of wild-type mice and in 83.3% of the PON1-deficient animals (P < 0.001). The metabolomic assay included 322 biochemical compounds, 169 of which were significantly decreased and 16 increased in PON1-deficient mice. There were significant increases in lipid peroxide concentrations and oxidative stress markers. We also found decreased glycolysis and the Krebs cycle. The urea cycle was decreased, and the pyrimidine cycle had a significant increase in orotate. The pathways of triglyceride and phospholipid synthesis were significantly increased. We conclude that PON1 deficiency is associated with oxidative stress and metabolic alterations leading to steatosis in the livers of mice receiving a high-fat high-cholesterol diet.
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Nicola Martinelli, Anabel Garcia-Heredia, Helena Roca, Nuria Aranda, Victoria Arija, Bharti Mackness, Michael Mackness, Fabiana Busti, Gerard Aragones, Juan Pedro-Botet, Federica Pedica, Ivana Cataldo, Judit Marsillach, Jorge Joven, Domenico Girelli, Jordi Camps (2013)  Paraoxonase-1 status in patients with hereditary hemochromatosis.   J Lipid Res Mar  
Abstract: Hereditary hemochromatosis (HH) is characterized by accumulation of iron, oxidative stress, inflammation and fibrogenesis in liver tissue. In this setting, research on the protection afforded by intracellular antioxidants is of clinical relevance. Paraoxonase1 (PON1) is an enzyme that degrades lipid peroxides. This study investigates the alterations in serum PON1 status, PON1 gene polymorphisms and PON1 hepatic expression in patients with HH. We performed a case-control study in 77 patients with HH (80.5% men, 22 to 70 years of age) and 408 healthy individuals (43.1% men, 26 to 74 years of age). Serum PON1 activities against different substrates and PON1192 and PON155 polymorphisms were analyzed. PON1 protein expression was investigated in 20 liver biopsies. HH patients had significantly lower serum PON1 activity, which was inversely correlated with ferritin (marker of iron stores) and serum 8isoprostane plasma concentrations (index of oxidative stress). PON1 protein expression in liver tissue was higher in patients, and showed stronger staining in hepatocytes surrounding the areas of inflammation. Our study provides preliminary evidence that PON1 may play a role in protecting against iron-induced oxidative stress in HH.
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Javier A Menendez, Jorge Joven, Gerard Aragonès, Enrique Barrajón-Catalán, Raúl Beltrán-Debón, Isabel Borrás-Linares, Jordi Camps, Bruna Corominas-Faja, Sílvia Cufí, Salvador Fernández-Arroyo, Anabel Garcia-Heredia, Ana Hernández-Aguilar, María Herranz-López, Cecilia Jiménez-Sánchez, Eugeni López-Bonet, Jesús Lozano-Sánchez, Fedra Luciano-Mateo, Begoña Martin-Castillo, Vicente Martin-Paredero, Almudena Pérez-Sánchez, Cristina Oliveras-Ferraros, Marta Rierra-Borrull, Esther Rodríguez-Gallego, Rosa Quirantes-Piné, Anna Rull, Laura Tomás-Menor, Alejandro Vazquez-Martin, Carlos Alonso-Villaverde, Vicente Micol, Antonio Segura-Carretero (2013)  Xenohormetic and anti-aging activity of secoiridoid polyphenols present in extra virgin olive oil: A new family of gerosuppressant agents.   Cell Cycle 12: 4. Jan  
Abstract: Aging can be viewed as a quasi-programmed phenomenon driven by the overactivation of the nutrient-sensing mTOR gerogene. mTOR-driven aging can be triggered or accelerated by a decline or loss of responsiveness to activation of the energy-sensing protein AMPK, a critical gerosuppressor of mTOR. The occurrence of age-related diseases, therefore, reflects the synergistic interaction between our evolutionary path to sedentarism, which chronically increases a number of mTOR activating gero-promoters (e.g., food, growth factors, cytokines and insulin) and the "defective design" of central metabolic integrators such as mTOR and AMPK. Our laboratories at the Bioactive Food Component Platform in Spain have initiated a systematic approach to molecularly elucidate and clinically explore whether the "xenohormesis hypothesis," which states that stress-induced synthesis of plant polyphenols and many other phytochemicals provides an environmental chemical signature that upregulates stress-resistance pathways in plant consumers, can be explained in terms of the reactivity of the AMPK/mTOR-axis to so-called xenohormetins. Here, we explore the AMPK/mTOR-xenohormetic nature of complex polyphenols naturally present in extra virgin olive oil (EVOO), a pivotal component of the Mediterranean style diet that has been repeatedly associated with a reduction in age-related morbid conditions and longer life expectancy. Using crude EVOO phenolic extracts highly enriched in the secoiridoids oleuropein aglycon and decarboxymethyl oleuropein aglycon, we show for the first time that (1) the anticancer activity of EVOO secoiridoids is related to the activation of anti-aging/cellular stress-like gene signatures, including endoplasmic reticulum (ER) stress and the unfolded protein response, spermidine and polyamine metabolism, sirtuin-1 (SIRT1) and NRF2 signaling; (2) EVOO secoiridoids activate AMPK and suppress crucial genes involved in the Warburg effect and the self-renewal capacity of "immortal" cancer stem cells; (3) EVOO secoiridoids prevent age-related changes in the cell size, morphological heterogeneity, arrayed cell arrangement and senescence-associated β-galactosidase staining of normal diploid human fibroblasts at the end of their proliferative lifespans. EVOO secoiridoids, which provide an effective defense against plant attack by herbivores and pathogens, are bona fide xenohormetins that are able to activate the gerosuppressor AMPK and trigger numerous resveratrol-like anti-aging transcriptomic signatures. As such, EVOO secoiridoids constitute a new family of plant-produced gerosuppressant agents that molecularly "repair" the aimless (and harmful) AMPK/mTOR-driven quasi-program that leads to aging and aging-related diseases, including cancer.
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2012
Anna Rull, Raúl García, Laura Fernández-Sender, Anabel García-Heredia, Gerard Aragonès, Raúl Beltrán-Debón, Judit Marsillach, Josep M Alegret, Vicente Martín-Paredero, Bharti Mackness, Michael Mackness, Jorge Joven, Jordi Camps (2012)  Serum paraoxonase-3 concentration is associated with insulin sensitivity in peripheral artery disease and with inflammation in coronary artery disease.   Atherosclerosis 220: 2. 545-551 Feb  
Abstract: There are no data on the relationship between serum paraoxonase-3 (PON3) concentration and atherosclerosis in humans. Our aim was to investigate possible associations, using recently developed methods, in patients with peripheral artery disease (PAD) or coronary artery disease (CAD).
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Jordi Camps, Anabel García-Heredia, Anna Rull, Carlos Alonso-Villaverde, Gerard Aragonès, Raúl Beltrán-Debón, Esther Rodríguez-Gallego, Jorge Joven (2012)  PPARs in Regulation of Paraoxonases: Control of Oxidative Stress and Inflammation Pathways.   PPAR Res 2012: 01  
Abstract: The paraoxonase (PON) group of enzymes, composed of PON1, PON2, and PON3, play an important role in decreasing oxidative stress by degrading lipid peroxides. PON1 synthesis is upregulated by PPAR. Several pharmacological compounds (acting as antioxidants and, hence, atheroprotective) stimulate both PPAR activity and PON1 expression. Recent evidence suggests that PON1 and the monocyte chemoattractant protein-1 (MCP-1) are involved in coordinating the inflammatory response in damaged tissues; PPAR may be central in the regulation of these biochemical pathways. This article reviews the state of knowledge on PON1 biochemistry and function, the influence of genetic variation, and the regulation of PON1 expression by pharmaceutical compounds that increase PPAR activity. We also describe recent lines of evidence suggesting links between PON1 and MCP-1 and how their production may be regulated by PPAR.
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Gerard Aragonès, Anabel García-Heredia, Marta Guardiola, Anna Rull, Raúl Beltrán-Debón, Judit Marsillach, Carlos Alonso-Villaverde, Bharti Mackness, Michael Mackness, Juan Pedro-Botet, Pedro Pardo-Reche, Jorge Joven, Jordi Camps (2012)  Serum paraoxonase-3 concentration in HIV-infected patients. Evidence for a protective role against oxidation.   J Lipid Res 53: 1. 168-174 Jan  
Abstract: We investigated the influence of the HIV infection on serum paraoxonase-3 (PON3) concentration and assessed the relationships with lipoprotein-associated abnormalities, immunological response, and accelerated atherosclerosis. We studied 207 HIV-infected patients and 385 healthy volunteers. Serum PON3 was determined by in-house ELISA, and PON3 distribution in lipoproteins was investigated by fast-performance liquid chromatography (FPLC). Polymorphisms of the PON3 promoter were analyzed by the Iplex Gold MassArray(TM) method. PON3 concentrations were increased (about three times) in HIV-infected patients with respect to controls (P < 0.001) and were inversely correlated with oxidized LDL levels (P = 0.038). Long-term use of nonnucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy was associated with a decrease of PON3 concentrations. In a multivariate linear regression analysis, these relationships were still strong when the main confounding covariates were considered. PON3 was mainly found in HDL in HIV-infected patients, but a substantial amount of the protein was detected in LDL particles. This study reports for the first time an important increase in serum PON3 concentrations in HIV-infected patients that is associated with their oxidative status and their treatment with NNRTI. Long-term, prospective studies are needed to confirm the possible influence of this enzyme on the course of this disease and its possible utility as an analytical biomarker.
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Jordi Camps, Anabel García-Heredia, Anna Rull, Carlos Alonso-Villaverde, Gerard Aragonès, Raúl Beltrán-Debón, Esther Rodríguez-Gallego, Jorge Joven (2012)  PPARs in Regulation of Paraoxonases: Control of Oxidative Stress and Inflammation Pathways.   PPAR Res 2012: 01  
Abstract: The paraoxonase (PON) group of enzymes, composed of PON1, PON2, and PON3, play an important role in decreasing oxidative stress by degrading lipid peroxides. PON1 synthesis is upregulated by PPAR. Several pharmacological compounds (acting as antioxidants and, hence, atheroprotective) stimulate both PPAR activity and PON1 expression. Recent evidence suggests that PON1 and the monocyte chemoattractant protein-1 (MCP-1) are involved in coordinating the inflammatory response in damaged tissues; PPAR may be central in the regulation of these biochemical pathways. This article reviews the state of knowledge on PON1 biochemistry and function, the influence of genetic variation, and the regulation of PON1 expression by pharmaceutical compounds that increase PPAR activity. We also describe recent lines of evidence suggesting links between PON1 and MCP-1 and how their production may be regulated by PPAR.
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Ahmed Djeghader, Gerard Aragonès, Nune Darbinian, Mikael Elias, Daniel Gonzalez, Anabel García-Heredia, Raúl Beltrán-Debón, Rafal Kaminski, Guillaume Gotthard, Julien Hiblot, Anna Rull, Olivier Rohr, Christian Schwartz, Carlos Alonso-Villaverde, Jorge Joven, Jordi Camps, Eric Chabriere (2012)  The level of DING proteins is increased in HIV-infected patients: in vitro and in vivo studies.   PLoS One 7: 3. 03  
Abstract: DING proteins constitute an interesting family, owing to their intriguing and important activities. However, after a decade of research, little is known about these proteins. In humans, at least five different DING proteins have been identified, which were implicated in important biological processes and diseases, including HIV. Indeed, recent data from different research groups have highlighted the anti-HIV activity of some DING representatives. These proteins share the ability to inhibit the transcriptional step of HIV-1, a key step of the viral cycle that is not yet targeted by the current therapies. Since such proteins have been isolated from humans, we undertook a comprehensive study that focuses on the relationship between these proteins and HIV-infection in an infectious context. Hence, we developed a home-made ELISA for the quantification of the concentration of DING proteins in human serum. Using this method, we were able to determine the concentration of DING proteins in healthy and HIV-infected patients. Interestingly, we observed a significant increase of the concentration of DING proteins in non treated and treated HIV-infected patients compared to controls. In addition, cell cultures infected with HIV also show an increased expression of DING proteins, ruling out the possible role of antiretroviral treatment in the increase of the expression of DING proteins. In conclusion, results from this study show that the organism reacts to HIV-infection by an overexpression of DING proteins.
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2011
Anabel García-Heredia, Judit Marsillach, Gerard Aragonès, Marta Guardiola, Anna Rull, Raúl Beltrán-Debón, Alba Folch, Bharti Mackness, Michael Mackness, Juan Pedro-Botet, Jorge Joven, Jordi Camps (2011)  Serum paraoxonase-3 concentration is associated with the severity of hepatic impairment in patients with chronic liver disease.   Clin Biochem 44: 16. 1320-1324 Nov  
Abstract: Research on paraoxonase-3 (PON3) has been hampered by the lack of methods for measurement. This is a pilot study aimed at exploring whether chronic liver impairment is associated with changes in serum PON3 concentrations, and to know whether this measurement may provide useful information to investigate this derangement.
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