Genetic determinants of endothelial cell heterogeneity
Endothelial cells line the inside of all blood vessels, playing a role in a multitude of physiological processes, including the control of cellular trafficking, the regulation of vasomotor tone, the maintenance of blood fluidity, and the growth of new blood vessels (Cines et al., 1998). It is important to recognize that the structure and function of endothelial cells differ in time and space (Garlanda and Dejana, 1997; Gerritsen, 1987; Page et al., 1992; Risau, 1995). As a general rule, endothelial cell phenotypes vary: 1) between different organs; 2) between different segments of the vascular loop within the same organ; and 3) between neighboring endothelial cells of the same organ and blood vessel type (Aird, 2001). For example, the von Willebrand factor gene is expressed predominantly within the endothelium of veins (Aird, 2001; Yamamoto et al., 1998), tissue factor pathway inhibitor is a marker for microvascular endothelium (Osterud et al., 1995), while thrombomodulin is expressed in the vasculature of all organs except the brain (Ishii et al., 1986). Recent in vivo phage display studies have uncovered a wide array of genes that are expressed in specific vascular beds of normal organs and tumors (Rajotte et al., 1998; Trepel et al., 2000). While endothelial cell complexity and diversity have long been recognized, little is known about the underlying molecular mechanisms that mediate phenotypic heterogeneity of different endothelial cell populations.