title: Enhanced reduction in oxidative stress and altered glutathione and thioredoxin system response to unsaturated fatty acid load in familial hypercholesterolemia.
abstract: OBJECTIVE
  Familial hypercholesterolemia (FH) is characterized by increased oxidative stress (OS) levels. In the postprandial state, lipids and lipoproteins modulate OS status through their impact on pro-oxidant and antioxidant mechanisms. The objective of this study was to evaluate in patients with FH the response to an unsaturated oral fat load test (OFLT) by analyzing the mRNA levels of genes involved in the glutathione and thioredoxin antioxidant systems.
  
  
  METHODS
  We analyzed 14 FH patients and 20 normolipidemic and normoglycemic controls. In both groups, mRNA values of antioxidant enzyme genes (glutathione and thioredoxin systems) were determined at baseline and at 2, 4, 6, and 8h after OFLT by real time PCR.
  
  
  RESULTS
  In the fasting state the mRNA levels of antioxidant enzymes GPX4 and the GSR, GSS, and GCLC enzymes (involved in glutathione regeneration and synthesis) and thioredoxin (TXN), were significantly increased in the FH group compared to the healthy controls. Some genes (GPX1 and GPX4) were increased at 4h in both groups, but values for the rest of the antioxidant enzyme mRNAs were decreased in FH patients after 4h from unsaturated OFLT and were increased in controls.
  
  
  CONCLUSIONS
  We concluded that an OFLT with predominantly unsaturated fat has a different effect on postprandial antioxidant enzyme mRNA levels in controls than in FH patients. Increased antioxidant enzyme mRNA is not the main way to reduce postprandial oxidative stress in FH. This difference could determine the influence of dietary patterns in these patients.
authors.affiliation: Genotyping and Genetic Diagnosis Unit, INCLIVA Biomedical Research Institute, Avd. Menendez Pelayo, 4 Accesorio, 46010 Valencia, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Cortes
authors.affiliation: Service of Endocrinology and Nutrition, Hospital Clinico Universitario, INCLIVA Biomedical Research Institute, Avd. Blasco Ibañez, 17, 46010 Valencia, Spain; CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona 08017, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Martinez-Hervas
authors.affiliation: Genotyping and Genetic Diagnosis Unit, INCLIVA Biomedical Research Institute, Avd. Menendez Pelayo, 4 Accesorio, 46010 Valencia, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Ivorra
authors.affiliation: Genotyping and Genetic Diagnosis Unit, INCLIVA Biomedical Research Institute, Avd. Menendez Pelayo, 4 Accesorio, 46010 Valencia, Spain.
authors.forename: Griselda
authors.initials: G
authors.lastname: De Marco
authors.affiliation: Genotyping and Genetic Diagnosis Unit, INCLIVA Biomedical Research Institute, Avd. Menendez Pelayo, 4 Accesorio, 46010 Valencia, Spain.
authors.forename: Veronica
authors.initials: V
authors.lastname: Gonzalez-Albert
authors.affiliation: UGCI of Endocrinology and Nutrition, IBIMA Biomedical Research Institute, Hospital Regional Universitario, Avd. Carlos Haya, 29010 Malaga, Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Rojo-Martínez
authors.affiliation: Department of Biochemistry and Molecular Biology-CIBEROBN Faculty of Medicine and Odontology-INCLIVA, 46010 Valencia, Spain; Service of Clinic Analysis, Dr. Peset University Hospital, University of Valencia, 2, 46014 Valencia, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Saez
authors.affiliation: Service of Endocrinology and Nutrition, Hospital Clinico Universitario, INCLIVA Biomedical Research Institute, Avd. Blasco Ibañez, 17, 46010 Valencia, Spain; CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona 08017, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Carmena
authors.affiliation: Service of Endocrinology and Nutrition, Hospital Clinico Universitario, INCLIVA Biomedical Research Institute, Avd. Blasco Ibañez, 17, 46010 Valencia, Spain; CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona 08017, Spain; Department of Medicine, University of Valencia, Avd. Blasco Ibañez, 17 46010 Valencia, Spain.
authors.forename: Juan F
authors.initials: JF
authors.lastname: Ascaso
authors.affiliation: Service of Endocrinology and Nutrition, Hospital Clinico Universitario, INCLIVA Biomedical Research Institute, Avd. Blasco Ibañez, 17, 46010 Valencia, Spain; CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona 08017, Spain; Department of Medicine, University of Valencia, Avd. Blasco Ibañez, 17 46010 Valencia, Spain. Electronic address: Jose.T.Real@uv.es.
authors.forename: Jose T
authors.initials: JT
authors.lastname: Real
authors.affiliation: Genotyping and Genetic Diagnosis Unit, INCLIVA Biomedical Research Institute, Avd. Menendez Pelayo, 4 Accesorio, 46010 Valencia, Spain; CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona 08017, Spain.
authors.forename: Felipe J
authors.initials: FJ
authors.lastname: Chaves
mesh_terms: D000328:Adult; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage*; D005215:Fasting; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005721:Glutamate-Cysteine Ligase / Q000235:genetics; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000235:genetics; D005980:Glutathione Reductase / Q000235:genetics; D005981:Glutathione Synthase / Q000235:genetics; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013879:Thioredoxins / Q000378:metabolism*
chemical_list: D004042:Dietary Fats, Unsaturated; C491203:TXN protein, human; D013879:Thioredoxins; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005721:Glutamate-Cysteine Ligase; D005981:Glutathione Synthase; D005978:Glutathione
keywords: Familial hypercholesterolemia; Glutathione enzymes; Oral fat load test; Oxidative stress; Thioredoxin enzymes; mRNA