VEGF gene expression in adult human thymus fat: a correlative study with hypoxic induced factor and cyclooxygenase-2.
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.


METHODS
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.


CONCLUSIONS
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.
Tinahones
Francisco
F
Centro de Investigación Biomédica en Red, Fisiopatología de la Obesidad y Nutrición (CB03/06), Instituto Carlos III, Madrid, Spain.
Salas
Julian
J
Mayas
María Dolores
MD
Ruiz-Villalba
Adrian
A
Macias-Gonzalez
Manuel
M
Garrido-Sanchez
Lourdes
L
DeMora
Manuel
M
Moreno-Santos
Inmaculada
I
Bernal
Rosa
R
Cardona
Fernando
F
El Bekay
Rajaa
R
D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D000273:Adipose Tissue / Q000201:enzymology* / Q000473:pathology; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002465:Cell Movement; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000166:cytology; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D040521:Subcutaneous Tissue / Q000378:metabolism / Q000473:pathology; D013950:Thymus Gland / Q000378:metabolism* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
D052242:Adiponectin; D000893:Anti-Inflammatory Agents; D015415:Biomarkers; C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D047495:PPAR gamma; D020033:Protein Isoforms; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D004247:DNA; D051547:Heme Oxygenase-1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human