The vascular endothelium lines the inside of all blood vessels. As such, it forms one of the largest internal surfaces that mediates the compartmentalization of the body. The endothelium thereby acts as interface between the blood and the different organs. Structurally, the endothelial layer is diverse and heterogeneous. It is organ and caliber specifically differentiated in a way that best serves the functional needs of the underlying tissue. For example, barrier-forming endothelia such as the brain and lung endothelium are continuous with numerous tight junctions that act as a permeability barrier. The endothelium in the kidneys is continuous, but has numerous fenestrae that facilitate the kidneys' filtration function. Sinusoidal endothelial cells (ECs) are discontinuous, allowing easy entry and exit of fluids and solutes.

The molecular analysis of organ- and caliber-specific EC differentiation is still in its infancy. A number of organ-specific. ECmolecules have been identified, such as endothelial-specific molecule (ESM)-1 as a marker of lung ECs (1) and the stabilins as markers of sinusoidal ECs (2). Yet, the functional role of such organ-specific EC molecules is not understood. Similarly, several caliber-specific ECmolecules have been identified in recent years. EphrinB2 is selectively expressed by arterial (and angiogenic) ECs, whereas EphB4 is preferentially expressed by venous ECs (3). Correspondingly, ephrinB2- and EphB4- deficient mice have essentially complementary embryonically lethal phenotypes characterized by perturbed arteriovenous differentiation (3). The asymmetric arteriovenous expression of ephrinB2 and EphB4 has stimulated research into the identification of EC molecules with arteriovenous asymmetric expression pattern. Some 20 arterial molecules (and much fewer venous-specific EC molecules) have been identified in the last 10 years. Correspondingly, gridlock and COUP-TFII have been characterized as transcription factors controlling arterial and venous EC differentiation, respectively (4,5).