Angiogenesis is critical for the development of all complex organisms (such as mammals) and occurs in several well-defined stages.
- Angiogenic growth factors activate receptors on endothelial cells which comprise the lining of blood vessel walls.
- Endothelial cells secrete enzymes called proteases allowing endothelial cells to form sprouts.
- Sprouts migrate toward the source of the angiogenic stimulus and form loops which develop vessel lumens.
- Growth factors then contribute to the consolidation of these newly formed blood vessels to form a fully functional vasculature.
- The vessels are then capable of delivering oxygen and nutrients to organs, thus sustaining their growth and development.
Therapeutic Angiogenesis Versus Pathological Angiogenesis
Regeneron scientists are identifying and validating molecular targets on endothelial cells which may modulate the process of angiogenesis.
- Therapeutic angiogenesis can be directed toward building new blood vessels in ischemic, chronic wounds where newly formed blood vessels can provide a conduit for oxygen and nutrients and can act as a means of removing damaged tissue and debris.
- Excessive or pathological angiogenesis is a major factor in numerous diseases ranging from cancer to rheumatoid arthritis, psoriasis, and endometriosis. Efforts are underway to examine whether VEGF is an important player in other diseases where pathological angiogenesis is involved.
Scientists in the angiogenesis group at Regeneron have identified numerous endothelial cell-specific genes using a transcriptional profiling database that are modulated during active angiogenesis and may become bona fide therapeutic angiogenesis targets.
Other Angiogenesis Targets
To validate antiangiogenic target candidates, Regeneron has leveraged the power of the VelociGene® technology to identify vascular-specific genes, including angiopoietin 2 and delta-like ligand 4 (Dll4).
Once candidates have been validated for further study, they will progress to the VelocImmune® platform where fully-human, monoclonal antibodies are made to examine the effects of activation and inhibition of these therapeutic targets.
Highlights
