Yale Researchers Discover VEGF Molecule Contributes to the Development of Asthma
In a whole new approach to asthma research, scientists at Yale have discovered that a molecule called Vascular Endothelial Growth Factor (VEGF) likely plays an important role in the development of the disease and raises the possibility of new asthma drugs that block VEGF receptors and signaling pathways.
VEGF is normally associated with the growth of new blood vessels in the lung and other organs. Yale researchers found, however, that in addition to this function, VEGF can also induce asthma-like abnormalities in the airway. When VEGF is expressed in the lungs of genetically engineered “transgenic” mice, asthma-like alterations develop, according to a report in the journal Nature Medicine.
“In humans with asthma, there is an increased level of VEGF, so we mimicked this condition in mice by over expressing VEGF in their lungs,” said principal investigator Jack A. Elias, M.D., section chief of pulmonary and critical care medicine at Yale School of Medicine. “To our surprise, in addition to growing new blood vessels, many other features of asthma were also seen in these mice. We saw mucous formation, airway fibrosis and asthma-like pulmonary function abnormalities. We also found that if you block VEGF, you block the asthma-like manifestations in other mouse asthma models.”
Previous studies showed that people with allergies and asthma have an excess of T-helper type 2 cells (TH2). Elias and his team found that when VEGF is produced, the TH2 response is increased.
A high percentage of people with asthma have allergies. They also have a higher tendency to become allergic to particles and antigens to which they are exposed. Normal individuals become tolerant to the same agents, instead of becoming allergic. “The reason why some people develop this tolerance and others don’t has never been understood,” Elias said. “We found that this tolerance is broken in the genetically-engineered transgenic mice, suggesting that the VEGF-induced break in tolerance contributes to the allergic sensitization of asthmatic patients.”
Elias and his team are currently examining how VEGF works at the cellular and molecular level. These latest findings add to the growing body of research from Elias’s lab that has advanced knowledge of asthma, a rapidly increasing chronic lung condition, which affects millions of people around the world.
Other authors on the study included Chun Geun Lee, M.D., Holger Link, M.D., Robert J. Homer, M.D., Svetlana Chapoval, M.D., Vineet Bhandari, M.D., Min Jong Kang, M.D., Lauren Cohn, M.D., and Yoon Keun Kim, M.D., of Yale; and Peter Baluk and Donald M. McDonald, M.D. of University of California/San Francisco.
Citation: Nature Medicine: Published online September 19, 2004