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Departments of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
1Correspondence: Beth Israel Deaconess Medical Center, Department of Pathology, RN 280 D, 330 Brookline Ave., Boston, MA 02215, USA. E-mail: evasile{at}caregroup.harvard.edu
VPF/VEGF acts selectively on the vascular endothelium to enhance permeability, induce cell migration and division, and delay replicative senescence. To understand the changes in gene expression during endothelial senescence, we investigated genes that were differentially expressed in early vs. late passage (senescent) human dermal endothelial cells (HDMEC) using cDNA array hybridization. Early passage HDMEC cultured with or without VPF/VEGF overexpressed 9 and underexpressed 6 genes in comparison with their senescent counterparts. Thymosin ß-10 expression was modulated by VPF/VEGF and was strikingly down-regulated in senescent EC. The ß-thymosins are actin G-sequestering peptides that regulate actin dynamics and are overexpressed in neoplastic transformation. We have also identified senescent EC in the human aorta at sites overlying atherosclerotic plaques. These EC expressed senescence-associated neutral ß-galactosidase and, in contrast to adventitial microvessel endothelium, exhibited weak staining for thymosin ß-10. ISH performed on human malignant tumors revealed strong thymosin ß-10 expression in tumor blood vessels. This is the first report that Tß-10 expression is significantly reduced in senescent EC, that VPF/VEGF modulates thymosin ß-10 expression, and that EC can become senescent in vivo. The reduced expression of thymosin ß-10 may contribute to the senescent phenotype by reducing EC plasticity and thus impairing their response to migratory stimuli.—Vasile, E., Tomita, Y., Brown, L. F., Kocher, O., Dvorak, H. F. Differential expression of thymosin ß-10 by early passage and senescent vascular endothelium is modulated by VPF/VEGF: evidence for senescent endothelial cells in vivo at sites of atherosclerosis.
Key Words: cDNA arrays • lipoproteins • human aorta
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