In rheumatoid arthritis, which is driven by reactive and inflammatory immune cells, a S1P1 inhibitor could block both immune and blood vessel-related mechanisms, and therefore may be beneficial, based on the study's findings. In addition, Dr. Hla points out that while the existing approved S1P1 inhibitor fingolimod has had some adverse effects in some multiple sclerosis patients, there are new inhibitors of S1P1 being developed by many companies that could also be tested in combination with a VEGF inhibitor for treating these diseases.
An Antenna that Senses Blood Flow
Angiogenesis is needed for many normal tissue growth, repair and regenerative processes, which ultimately results in increased blood flow and oxygenation of tissues.
The Hla laboratory has long been interested in defining the molecular mechanisms of the angiogenic process, in which endothelial cells from pre-existing blood vessels sprout, move and then change to form new vascular channels. Dr. Hla was first to identify S1P1 as a key angiogenic response gene, and he also successfully cloned and characterized the receptor.
In this study, the research team shows that as new blood vessel networks form, the resulting blood flow activates S1P1 on the surface of endothelial cells and relays signals inside these cells to stabilize new blood vessel networks.
"The S1P1 molecule acts like an antenna to sense blood flow. If blood flow is reduced, then normal S1P1 signaling is interrupted, destabilizing blood vessel formation, causing the endothelium to undergo an inflammatory process," Dr. Hla says. "This happens in many diseases with abnormal vessels, including rheumatoid arthritis, psoriasis and even cancer."
In their laboratory studies, the researchers found that blocking S1P1 resulted in abnormal endothelial function and blood vessel growth. In
|Contact: Lauren Woods|
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College