Tinahones, Francisco JSalas, JulianMayas Torres, María DoloresRuiz-Villalba, AdriánMacías-González, ManuelGarrido-Sánchez, LourdesDeMora, ManuelMoreno-Santos, InmaculadaBernal, RosaCardona Díaz, FernandoEl Bekay, Rajaa2012-12-072012-12-072009-12-14Tinahones F, Salas J, Mayas MD, Ruiz-Villalba A, Macias-Gonzalez M, Garrido-Sanchez L, et al. VEGF gene expression in adult human thymus fat: a correlative study with hypoxic induced factor and cyclooxygenase-2. PLoS ONE; 4(12):e8213http://hdl.handle.net/10668/693Journal Article; Research Support, Non-U.S. Gov't;It is well known that the adult human thymus degenerates into fat tissue; however, it has never been considered as a potential source of angiogenic factors. Recently, we have described that this fat (TAT) produces angiogenic factors and induces human endothelial cell proliferation and migration, indicating its potential angiogenic properties. DESIGN Adult thymus fat and subcutaneous adipose tissue specimens were obtained from 28 patients undergoing cardiac surgery, making this tissue readily available as a prime source of adipose tissue. We focused our investigation on determining VEGF gene expression and characterizing the different genes, mediators of inflammation and adipogenesis, and which are known to play a relevant role in angiogenesis regulation. RESULTS We found that VEGF-A was the isoform most expressed in TAT. This expression was accompanied by an upregulation of HIF-1alpha, COX-2 and HO-1 proteins, and by increased HIF-1 DNA binding activity, compared to SAT. Furthermore, we observed that TAT contains a high percentage of mature adipocytes, 0.25% of macrophage cells, 15% of endothelial cells and a very low percentage of thymocyte cells, suggesting the cellular variability of TAT, which could explain the differences in gene expression observed in TAT. Subsequently, we showed that the expression of genes known as adipogenic mediators, including PPARgamma1/gamma2, FABP-4 and adiponectin was similar in both TAT and SAT. Moreover the expression of these latter genes presented a significantly positive correlation with VEGF, suggesting the potential association between VEGF and the generation of adipose tissue in adult thymus. CONCLUSION Here we suggest that this fat has a potential angiogenic function related to ongoing adipogenesis, which substitutes immune functions within the adult thymus. The expression of VEGF seems to be associated with COX-2, HO-1 and adipogenesis related genes, suggesting the importance that this new fat has acquired in research in relation to adipogenesis and angiogenesis.enFABP4 protein, humanPPAR gammaProtein IsoformsVEGFA protein, humanCyclooxygenase 2PTGS2 protein, humanPPAR gammaIsoformas de ProteínasCiclooxigenasa 2Tejido adiposoAntiinflamatoriosMarcadores BiológicosMovimiento CelularCiclooxigenasa 2ADNProteínas de Unión a Ácidos GrasosRegulación de la Expresión GénicaHemo-Oxigenasa 1Hipoxia InducibleInflamaciónMacrófagosUnión proteicaIsoformas de proteínasARN MensajeroTejido subcutáneoTimoFactor A de crecimiento endotelial vascularAdiponectinaMedical Subject Headings::Anatomy::Tissues::Connective Tissue::Adipose TissueMedical Subject Headings::Named Groups::Persons::Age Groups::AdultMedical Subject Headings::Named Groups::Persons::Age Groups::Adult::AgedMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Inflammatory AgentsMedical Subject Headings::Chemicals and Drugs::Biological Factors::Biological MarkersMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell MovementMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Multienzyme Complexes::Prostaglandin-Endoperoxide Synthases::Cyclooxygenase 2Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Nucleic Acid ConformationMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Carrier Proteins::Fatty Acid-Binding ProteinsMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression RegulationMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Oxidoreductases::Oxygenases::Mixed Function Oxygenases::Heme Oxygenase (Decyclizing)Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription Factors::Basic Helix-Loop-Helix Transcription Factors::Hypoxia-Inducible Factor 1Medical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::InflammationMedical Subject Headings::Anatomy::Cells::Connective Tissue Cells::MacrophagesMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Protein BindingMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Protein IsoformsMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, MessengerMedical Subject Headings::Anatomy::Tissues::Connective Tissue::Subcutaneous TissueMedical Subject Headings::Anatomy::Tissues::Lymphoid Tissue::Thymus GlandMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Angiogenic Proteins::Vascular Endothelial Growth Factors::Vascular Endothelial Growth Factor AMedical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Adipokines::AdiponectinVEGF gene expression in adult human thymus fat: a correlative study with hypoxic induced factor and cyclooxygenase-2.research article20011601open access10.1371/journal.pone.00082131932-6203PMC2788242