This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Human umbilical vein endothelial cells (EC) that are isolated from umbilical cords are used to pursue the central objective to understand the role of gene expression by vascular EC in the physiological maintenance of vessel wall homeostasis and in the pathological development of the atherosclerotic lesion. Two specific research areas are under investigation. The first area focuses on the regulation of expression of leukocyte adhesion proteins, including E-selectin and VCAM-1, by the endothelium in response to thrombin, cytokines and the viral mimetic double-stranded RNA. The second area is the regulation of expression of the platelet-derived growth factor (PDGF)A and B chain genes by EC. In many of our studies human foreskin fibroblasts are employed as a control cell type due to their very different properties from EC. Other experiments are performed related to the ability of oxidized LDL to injure or alter function of various cell types, including human foreskins fibroblast and human umbilical vein endothelial and smooth muscle cells grown in tissue culture to include signaling pathways by which oxidized LDL and its constituent lipids (particularly various oxysterols) induce apoptosis. This study use foreskins and umbilical vein, which would otherwise be discarded, from which cultured fibroblasts, endothelial cells and smooth muscle cells are grown. There is no risk to individuals.
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