Growth factors acting via endothelial cell-specific receptor tyrosine kinases: VEGFs, Angiopoietins, and ephrins in vascular development

  1. Nicholas W. Gale and
  2. George D. Yancopoulos
  1. Regeneron Pharmaceuticals, Inc., Tarrytown, New York 10591-6707 USA

This extract was created in the absence of an abstract.

The term ‘vasculogenesis’ refers to the earliest stages of vascular development, during which vascular endothelial cell precursors undergo differentiation, expansion, and coalescence to form a network of primitive tubules (Risau 1997). This initial lattice, consisting purely of endothelial cells that have formed rather homogenously sized interconnected vessels, has been referred to as the primary capillary plexus. The primary plexus is then remodeled by a process referred to as angiogenesis (Risau 1997), which involves the sprouting, branching, and differential growth of blood vessels to form the more mature appearing vascular patterns seen in the adult organism. This latter phase of vascular development also involves the sprouting and penetration of vessels into previously avascular regions of the embryo, and also the differential recruitment of associated supporting cells, such as smooth muscle cells and pericytes, as well as fibroblasts, to different segments of the vasculature (Folkman and D’Amore 1996; Lindahl et al. 1997). The adult vascular network is comprised of large arteries, internally lined by endothelial cells and well ensheathed by smooth muscle cells, that progressively branch into smaller and smaller vessels, terminating in precapillary arterioles that then give rise to capillaries. Capillaries are comprised almost entirely of endothelial cells that are only occasionally coated by a smooth muscle cell-like pericyte. Capillaries then feed into postcapillary venules that progressively associate into larger and larger venous structures; venous structures are fully enveloped by smooth muscle cells, though not to the same degree as arterial structures.

The development of a functioning vascular network requires a remarkable degree of coordination between different cell types undergoing complex changes, and is exquisitely dependent upon signals exchanged between these cell types. Vascular endothelial growth factor (VEGF-A) provided the first example of a growth factor specific for the vascular endothelium, and VEGF-A has since been shown to be a …

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