Mechanism Identified that Modulates Blood Vessel Growth

Researchers have characterized the molecular mechanism whereby the body controls the growth of new blood vessels. This mechanism fails to function during rapid growth of tumors or in diabetic retinopathy and macular degeneration, the leading causes of blindness in the Western world.

New blood vessel growth or angiogenesis is controlled by the interaction of factors acting either to induce or inhibit proliferation of the endothelial cells that form the walls of new blood vessels. In a report published in the April 2002 issue of Nature Medicine, scientists from Northwestern University (Chicago IL, USA) and Washington University (St. Louis MO, USA) explain why certain natural inhibitors administered as drugs against angiogenesis-dependent diseases like cancer and diabetic retinopathy selectively destroy only newly formed vessels, not preexisting ones.

In the study, endothelial cells activated by an inducer expressed a cell surface protein receptor called Fas, which made the cells sensitive to the inhibitors in their environment. The inhibitors, thrombospondin-1 (TSP1) or pigment epithelial-derived factor (PEDF) activated a ligand, another cell surface protein called FasL, initiating a molecular cascade that resulted in death of the cell.

It has been known for some time that Fas/FasL interactions target immune cells for destruction in immune-privileged and diseased tissues when large populations of cells are to be eliminated. The results of the current study show that these interactions also affect the fate of vascular tissues where new vessels are subject for destruction by inhibitors of angiogenesis. These results indicate that the angiogenesis-inhibiting activity of TSP1 and PEDF was dependent on the dual induction of Fas and FasL as well as on the resulting apoptosis. Furthermore, TSP1 and PEDF reduced the expression of the inducer-stimulated molecule that blocks apoptosis.

This cooperation between pro- and anti-angiogenic factors may have major implications on the therapeutic use of these two inhibitors. Fas and its ligand may serve as new targets to design anti-angiogenic drugs or to improve already existing drugs.



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