ABSTRACT

Until recently, molecular diversity of the vasculature remained largely unexplored. In the past, the circulatory system had been assumed to consist of vessels that serve a universal transport function throughout the organism and that are, therefore, morphologically and biochemically undistinguishable in different organs. Lately, it has become clear, however, that the morphology of microvessels can vary drastically among different tissues. Capillary shape and the content of supporting cells (pericytes) in pathological (tumors), as well as in physiological (adipose tissue) conditions, may drastically differ from those in other tissues. Recently, it has become apparent that vascular beds of different organs can be distinguished at the molecular level. This variability results in tissue-specific differences in binding of circulating molecules and cells to the endothelium. Thus, the combination of anatomical context, tissue-specifically expressed endothelial receptors, and the surrounding extracellular matrix creates unique microvascular environments among different organs. Vascular mapping involves identification and characterization of such variables, termed vascular addresses, which, as discussed below, often turn out to be endothelial cell surface proteins that show tissue-specific expression patterns. A proteome map of the circulatory system is much awaited because characterization of endothelial receptors will help to understand how specific circulating molecules, cells, or pathogens are directed to individual organs. Characterization of vascular addresses or “zip codes” will also provide the means for unraveling the molecular mechanisms of vascular disorders and for targeting therapies to specific organs (Arap et al., 1998a; Folkman, 2002; Narasimhan, 2002; Rubin and Tall, 2000).