Regional specialization of endothelial cells as revealed by genomic analysis
The vascular system is locally specialized to accommodate widely varying needs of individual tissues. The regional specialization of vascular structure is closely linked to the topographic differentiation of endothelial cells (ECs). The gene expression programs that characterize specific ECs define their physiological specialization and their role in the development of vascular channels and epithelial organs. Our understanding of EC regional differentiation is very limited. To assess the heterogeneity of ECs on a global scale, we used DNA microarrays to obtain the global gene expression profiles of more than 50 cultured ECs purified from 14 different anatomic locations. We found that ECs from different blood vessels and microvascular ECs from different tissues have distinct and characteristic gene expression profiles. Pervasive differences in gene expression patterns distinguish the ECs of large vessels from microvascular ECs. We identified groups of genes characteristic of arterial and venous endothelium. Hey2, the human homolog of the zebrafish gene gridlock, was expressed only in arterial ECs and could trigger arterial-specific gene expression programs when introduced into venous ECs. Several genes critical in the establishment of left-right asymmetry were expressed preferentially in venous ECs, suggesting a surprising link between vascular differentiation and body plan development. Tissue-specific expression patterns in different tissue microvascular ECs suggest they are distinct differentiated cell types that play roles in the local physiology of their respective organs and tissues. Therefore, ECs from different anatomical locations constitute many distinct, differentiated cell types that carry out unique genetic programs to specify the site-specific design and functions of blood vessels to control internal body compartmentalization, regulate the trafficking of circulating cells, and shape the vascular development. In this chapter, we discuss these findings and their implications in different aspects of vascular biology during development and vascular diseases. © 2007 Humana Press Inc.