Increased expression of extracellular proteins as a hallmark of human endothelial cell in vitro senescence
| Autor: | Klaus Fortschegger, Martina Wei-Fen Chang, Pidder Jansen-Dürr, Günter Lepperdinger, A. Breitwieser, B. Fitzky, Hermann Unterluggauer, S. Ressler, Regina Voglauer, Barbara Hampel, W. Sommergruber, Johannes Grillari |
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| Rok vydání: | 2006 |
| Předmět: |
Tumor Necrosis Factor Ligand Superfamily Member 15
Senescence Umbilical Veins Aging Blotting Western Apoptosis Biology Biochemistry Endocrinology Western blot Downregulation and upregulation Genetics medicine Humans Interleukin 8 Molecular Biology Cells Cultured Cellular Senescence medicine.diagnostic_test Reverse Transcriptase Polymerase Chain Reaction Interleukin-8 Endothelial Cells Cell Biology Molecular biology In vitro Up-Regulation Cell biology Insulin-Like Growth Factor Binding Proteins Endothelial stem cell Vascular endothelial growth factor B Protein Biosynthesis Endothelium Vascular |
| Zdroj: | Experimental Gerontology. 41:474-481 |
| ISSN: | 0531-5565 |
| DOI: | 10.1016/j.exger.2006.03.001 |
| Popis: | A convenient way to study processes of aging in distinct human tissues consists of a molecular analysis of cells from the tissue in question, that were explanted and grown in vitro until they reach senescence. Using human umbilical vein endothelial cells (HUVEC), we have established an in vitro senescence model for human endothelial cells. A major hallmark of HUVEC in vitro senescence is the increased frequency of apoptotic cell death, which occurs as a determining feature of HUVEC senescence. Senescent endothelial cells are also found in vivo in atherosclerotic lesions, suggesting that the presence of such cells may contribute to the development of vascular pathology. To elucidate mechanisms underlying endothelial cell senescence and age-associated apoptosis, gene expression analyses were carried out. In these experiments, we observed the up-regulation of genes coding for extracellular proteins in senescent HUVEC. In particular, a significant upregulation of interleukin-8, VEGI, and the IGF-binding proteins 3 and 5 was observed. Upregulation of these genes was confirmed by both RT-PCR and Western blot. In the case of interleukin-8, a roughly 50-fold upregulation of the protein was also found in cellular supernatants. The extracellular proteins encoded by these genes are well known for their ability to modulate the apoptotic response of human cells, and in the case of interleukin-8, clear links to the establishment of atherosclerotic lesions have been defined. The results described here support a new model, where changes in the secretome of human endothelial cells contribute to vascular aging and vascular pathology. |
| Databáze: | OpenAIRE |
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