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Built-in 'failsafe' device blocks abnormal growth of new blood vessels

CHICAGO --- Some inhibitors of angiogenesis prevent new blood vessel growth by triggering a built-in "failsafe" device in vessel-forming endothelial cells that marks them for apoptosis, or programmed cell death, according to a study from The Feinberg School of Medicine at Northwestern University and Washington University at St. Louis.

By identifying the molecular mechanisms that control this failsafe device, it may be possible to design new anti-angiogenic drugs or to improve already existing drugs to prevent abnormal blood vessel growth, says Olga Volpert, assistant professor of urology at the Feinberg School and lead author the study, which appeared in the April issue of the journal Nature Medicine.

Angiogenesis, or aberrant growth of new blood vessels, enables cancerous tumors to spread through the body and also causes diabetic retinopathy and macular degeneration, the leading causes of blindness in the Western world.

Research has shown that new blood vessel growth relies on an exquisite balance of proteins that either induce or inhibit new growth of the endothelial cells that form the walls of new blood vessels. Identifying the components that influence this balance thus has major scientific relevance for understanding angiogenesis-dependent diseases and for developing therapies to prevent neovascularization.

When certain natural inhibitors are administered as drugs against angiogenesis-dependent diseases like cancer and diabetic retinopathy, they selectively destroy only newly formed vessels, not preexisting ones -- for reasons that were unclear until now.

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 its ligand, another cell surface protein called FasL -- which fits into the Fas re
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Contact: Elizabeth Crown
e-crown@northwestern.edu
312-503-8928
Northwestern University
11-Apr-2002


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