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oai:repisalud.isciii.es:20.500.12105/170122024-11-28T14:56:28Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927

00925njm 22002777a 4500 dc Tinahones Madueño, Francisco José author Salas, Julian author Mayas Torres, María Dolores author Ruiz-Villalba, Adrián author Macías-González, Manuel author Garrido-Sánchez, Lourdes author DeMora, Manuel author Moreno-Santos, Inmaculada author Bernal, Rosa author Cardona Díaz, Fernando author El Bekay, Rajaa author 2009-12-14 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. 10.1371/journal.pone.0008213 1932-6203 PloS one http://hdl.handle.net/10668/693 20011601 http://hdl.handle.net/20.500.12105/17012 FABP4 protein, human PPAR gamma Protein Isoforms VEGFA protein, human Cyclooxygenase 2 PTGS2 protein, human PPAR gamma Isoformas de Proteínas Ciclooxigenasa 2 Tejido adiposo Antiinflamatorios Marcadores Biológicos Movimiento Celular Ciclooxigenasa 2 ADN Proteínas de Unión a Ácidos Grasos Regulación de la Expresión Génica Hemo-Oxigenasa 1 Hipoxia Inducible Inflamación Macrófagos Unión proteica Isoformas de proteínas ARN Mensajero Tejido subcutáneo Timo Factor A de crecimiento endotelial vascular Adiponectina VEGF gene expression in adult human thymus fat: a correlative study with hypoxic induced factor and cyclooxygenase-2.