Transcription factors play a pivotal role in the coupling of endothelial gene expression to endothelial function. The tightly controlled regulation of endothelial gene expression is required for several aspects of endothelial biology. During embryogenesis, for example, the normal development of a primary vascular network, or vasculogenesis, requires a series of carefully orchestrated events that are spatially and temporally regulated. These events are largely coordinated by the precisely timed expression of selected sets of transcription factors. In the adult, endothelial cell (EC)-specific genes are differentially regulated in different body organs or tissues. These differences are in large part dependent on paracrine interactions between tissue-specific cell types and the endothelium. These paracrine interactions depend on the coupling of one cell type with another and are largely mediated by specific transcriptional programs. Under changing environmental or pathological conditions, the endothelium in the affected organ or tissue undergoes distinct changes in gene expression. The identification of specific transcription factors involved in the regulation of the endothelium under normal and pathological conditions not only has led to a better understanding of basic underlying mechanisms of endothelial gene regulation, but alsomay provide novel therapeutic targets for treating patients with a variety of diseases. Indeed, recent studies have demonstrated the feasibility of targeting transcription factors using small molecules (discussed in the section Therapeutic Implications).

We and other investigators have recently demonstrated the importance of selected members of the Ets transcription factor family in regulating endothelial-specific gene expression during normal development, in mediating vascular-bed specific expression in adult endothelium, and in modulating the expression of activation markers under pathological conditions.