Considerations on the mechanism of the angiogenic response.

The principal objective of our work is to sufficiently understand the mechanism of angiogenesis in the adult organism to allow interference with the process on a rational basis. It is apparent that several "factors" can trigger angiogenesis. To test these, we used the rabbit cornea mostly because it is avascular (i.e., the background is zero) and transparent (i.e., the newly formed capillaries that invade the cornea are easily visible in the unanaesthetized animal). Under these conditions, it was found that the cornea ready to be colonized by capillaries under the action of an angiogenesis effector becomes rich in copper ions and sialic acid. Motility of bovine capillary endothelium was utilized to analyze the angiogenesis process on the ground that mobilization of capillary endothelium is the first morphological event observed during angiogenesis in vivo and the methods to measure cell motility are reasonably accurate. With this approach it was found that heparin, fibronectin, and gangliosides are involved in the mobilization of capillary endothelium. The precise interaction among these three components is not yet clear.