While these genes were repressed at senescence, microarray analysis demonstrated overexpression of immuneresponse and inflammatory genes in early passage HUVEC. After 1 week of inhibition, shortening of telomeres wasn’t yet seen in this study. We also demonstrate that JZL184 dissolve solubility direct inhibition of PKC and PI3K/Akt, which are downstream signal transducers of VEGF and mediate survival and proliferation signals in endothelial cells, similarly induce premature senescence, reduction of telomerase activity, and increased expression of p21. These results suggest that induction of premature senescence by SU5416 and another TKIs that were used in this study may be through inhibition of these intracellular mediators. It remains to be determined whether early senescence is mediated by selective inhibition of VEGFR 2 phosphorylation. SU5416, even though thought to be a selective TKI, also exhibits concentration dependent inhibition of other growth factor receptors, such as the fibroblast growth factor receptor, VEGF receptor 1, insulin like growth factor I receptor, Stem Cell Factor Receptor d set, and hepatocyte growth factor receptor as well as intracellular kinases, PTM such as sarcoma. Thus, the other TKIs and SU5416 may induce premature senescence by functioning on several growth factormediated pathways or even by other unknown mechanisms in addition to the tyrosine kinases. Subsequent permanent expansion arrest, little is known in regards to the destiny of senescent endothelial cells. First, it is unclear how premature senescence and apoptosis relate solely to one another. In a single survey, senescent HUVEC, charged in the G1 phase of the cell cycle, displayed a substantial increase in spontaneous apoptosis and were also more prone to drug-induced apoptosis, indicating that senescence may aid apoptosis. In still another report, the rate of apoptosis remained unchanged through the process of senescence. Second, do senescent cells remain metabolically active and do they retain functional properties? Senescent fibroblasts mixed k63 ubiquitin with altered epithelial cells stimulated the growth of the latter in vitro and in tumor models. Tumefaction cells senescing in a reaction to chemotherapy secreted proteins with anti-apoptotic, mitogenic, and angiogenic activities. On the positive side, senescent cells may also inhibit growth of cancer or other neighboring nonsenescent cells by secreting growth inhibitory substances. We have shown that senescent OECs have reduced degrees of VEGFR 2 and to VEGF alone and CXCR 4, which may cause a lesser responsiveness to the ligands, as shown by paid down migratory ability to EGM 2MV. In senescent OECs, we did not find changes in endothelial adhesion molecules, such as for instance ICAM 1, an integral protein in leukocyte transendothelial migration previously reported to amass in senescent endothelial cells.