A phage display perspective

The vascular system is a complex network of vessels connecting the heart with organs and tissues to maintain homeostasis in response to physiological and pathological stimuli. Blood vessels are composed of endothelial cells (ECs), mural cells (pericytes or smooth muscle cells), and basement membrane. ECs lining the inner surface of blood and lymphatic vessels play important roles in the control of vascular tone, hemostasis, tissue growth, capillary exchange, inflammation, immune response, and angiogenesis. Even though these functions, along with other anatomical and molecular features, are common to all ECs, substantial structural and functional heterogeneity is seen among them. For example, ECs in the brain form a tight continuous monolayer required for a critical barrier function (blood–brain barrier), but those in the kidney, spleen, liver, and bone marrow display fenestrations or intercellular gaps for the rapid exchange of fluids and/or cells. This diversity is clearly a result of molecular differences between EC populations, which allow complex interactions with very distinctive microenvironments. Recent studies have identified transcriptional diversity between ECs in different types of blood vessels (arteries vs. veins, vessels of different caliber) and different anatomical locations (1–4).Not surprisingly, lymphatic ECs also display distinct characteristics (5). Blood vessels can grow from endothelial progenitors (vasculogenesis), from the sprouting and subsequent stabilization of these sprouts by mural cells (angiogenesis and arteriogenesis), or from the expansive growth of preexisting vessels (collateral growth) (6). When vessel growth is altered, in particular when excessive angiogenesis occurs, new blood vessels contribute to a long (and growing) list of disorders, including cancer, arthritis, retinopathies, obesity, atherosclerosis, and asthma (6). However, it is in solid tumors where an abnormal vasculature is a hallmark (7, 8).