The development of collateral vascularization following femoral artery resection is attributed it to reduced. Our data complement these observations, and suggest that the effects of senescence are somewhat more complex and entail abnormal response to physiological regulators of angiogenesis as well. Of particular interest is the previously unreported decline in LOX-1 transcription as endothelial cells age. In the present study, the reduction in LOX-1 was dramatic in late passage endothelial cells, and this phenomenon was confirmed in the endothelial lining of aortas of old mice. LOX-1 is a primary scavenger receptor in endothelial cells and plays a significant role in a variety of endothelial functions. Recent studies by our group have implicated LOX-1 in the stimulation of angiogenesis via activation of NADPH oxidase and consequent increase in ROS production. The role of LOX-1 in mediation of pro-angiogenic action of small concentrations of ox-LDL and angiotensin II was elucidated utilizing NADPH oxidase inhibitors and LOX-1 abrogation, and it can be expected, therefore, that depletion of LOX-1 in the senescent endothelial cells would contribute to depressed angiogenic potential. We also observed that endothelial senescence was associated with enhanced cell apoptosis which may have implications in reduced angiogenesis. We examined ox-LDL-mediated apoptosis and it was not affected in the P12 cells, most likely reflecting a deficit of LOX-1 which is required for ox-LDLinduced apoptosis. There was, however, a significant increase in TNFa-induced apoptosis in the older endothelial cells. The altered pattern of apoptosis was associated with changes in BAX and BCL2 expression, suggesting that these mediators of apoptosis are also adversely affected by the aging process. A pro-apoptotic shift appears to be typical of senescence, and increased susceptibility to apoptosis has been reported for variety of cell types including fibroblasts, myocytes, epithelial and endothelial cells. The reported hypersensitivity of endothelial cells to TNFa by Hoffman et al is similar to our results; however, enhancement of apoptosis in response to ox-LDL observed in the same study is different from our results and counters the expectations based on the decline of LOX-1 expression in senescent cells. These authors, however, did not provide information on the concentration of ox-LDL used for their experiments which, if beyond the physiological limits, could exert non-specific cytotoxicity. Mice have long been invaluable in helping immunologists to understand how immunity works, especially when systemic effects of immune modulations were studied. Many immunotherapeutic approaches, such as neutralization of inflammatory cytokines for treatment of autoimmune disease have been pioneered in mice. Despite many similarities, differences exist between the human and murine immune system. Both human and murine monocytes express CD137 ligand, a member of the TNF superfamily. CD137 ligand not only sends signals to CD137-expressing cells but it is a transmembrane Cinoxacin protein on the cell surface that can also deliver signals into the cells it is expressed on,. Peripheral human monocytes are activated by CD137 ligand signaling, evidenced by enhanced Sertraline hydrochloride adherence, increased expression of ICAM-1 and secretion of proinflammatory cytokines, increased survival, induction of proliferation and enhanced migration.