Many pathophysiologic changes recapitulate processes which also occur during embryogenesis. One focus of our laboratory is to use the tools of molecular genetics and embryology, especially in the mouse, to understand how the functional maturation and diversification of the vascular system in adults is intially specified during ontogeny and later modulated during various disease processes.
We have concentrated on the inflammatory cytokine activation response of vascular endothelium for several reasons. First, endothelium plays an important role in orchestrating, as well as implementing, the functional diversity which characterizes the vascular beds of different tissues and organs. In addition, cytokine activation responses can be conveniently and specifically assayed both at the level of gene expression as well as at the level of functional consequences in inflammatory processes. These studies have identified several stages in developmental maturation of the E-selectin response to stimulation by inflammatory cytokines.2