For many years structural and functional differences in endothelial cells have been recognized among organs, and between specialized sites, such as in high endothelial venules. More recently, however, phenotypic variation in endothelial structure and function along a single blood ves sel has been examined. These results illustrate a heterogeneity that arises not only because of the environment in which the cell resides, but also because of the cell's origin. Indeed, endothelial cells become imprinted in the course of development, as do all cells, based upon their interactions with surrounding tissue environments to achieve differentiation. As this differentiated phenotype is stable through mitotic cell divisions, the cell retains a memory from whence it came even through multiple passages in tissue culture. We are only now beginning to appreciate the significance of these epigenetic modifications in endothelial function and their relevance to site-specific disease susceptibility. Subsequent investigation will provide significant insight into how normal lung vascular development imprints on macro- and microvascular endothelial cells a phenotype that is uniquely suited to fulfill their site-specific functions.

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