Figure 22–24 Angiogenesis. (a) a new blood capillary forms by the sprouting of an endothelial cell from the wall of an existing small vessel. an endothelial tip cell, with many filopodia, leads the advance of each capillary sprout. the endothelial stalk cells trailing behind the tip cell become hollowed out to form a lumen. (b) blood capillaries sprouting in the retina of an embryonic mouse that had a red dye injected into the bloodstream, revealing the capillary lumen opening up behind the tip cell (Movie 22.2). (b, from h. Gerhardt et al., J. Cell Biol. 161:1163–1177, 2003. with permission from the author.) pericytes clinging 10 µmto outer face of small blood vessel
Figure 22–23 Pericytes. the scanning electron micrograph shows pericytes wrapping their processes around a small blood vessel (a post-capillary venule) in the mammary gland of a cat. pericytes are also present around capillaries, but are much more sparsely distributed there. (From t. Fujiwara and y. uehara, Am. J. Anat. 170:39–54, 1984. with permission from wiley-liss.) those of a neuronal growth cone. The column of stalk cells behind it, meanwhile, becomes hollowed out to form a lumen.
The endothelial tip cells that pioneer the growth of normal capillaries not only look like neuronal growth cones, but also respond similarly to signals in the environment. In fact, many of the same guidance molecules are involved, including the netrins, slits, and ephrins mentioned in our account of neural development in the previous chapter. The corresponding receptors are expressed in the tip cells and guide the vascular sprouts along specific pathways in the embryo, often in parallel with nerves. Perhaps the most important of the guidance molecules for endothelial cells, however, is one that is chiefly dedicated to the control of vascular development: vascular endothelial growth factor, or VEGF.
Almost every cell, in almost every tissue of a vertebrate, is located within 50–100 μm of a blood capillary. What mechanism ensures that the system of blood vessels branches into every nook and cranny? How is it adjusted so perfectly to the local needs of the tissues, not only during normal development but also in pathological circumstances? Wounding, for example, induces a burst of capillary growth in the neighborhood of the damage, to satisfy the high metabolic requirements of the repair process (Figure 22–25). Local irritants and infections also cause a proliferation of new capillaries, most of which regress and disappear when the inflammation subsides. Less benignly, a small sample of tumor tissue implanted in the cornea, which normally lacks blood vessels, causes blood vessels to grow quickly toward the implant from the vascular margin of the cornea; the growth rate of the tumor increases abruptly as soon as the vessels reach it.