VEGF contributes to asthma development
vascular endothelial growth factor (VEGF) plays an important role
in the development of the disease and raises the possibility of new
asthma drugs that block VEGF receptors and signalling pathways.
In this new approach to asthma, the scientists discovered that when VEGF is expressed in the lungs of genetically engineered transgenic mice, asthma-like alterations developed. VEGF is normally associated with the growth of new blood vessels in the lung and other organs.
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.
Jack Elias, principal investigator of this study said: "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."
"In additon to growing new blood vessels, many other features of asthma were also seen in these mice. We observed 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."
A high percentage of people with asthma have allergies suggesting a higher tendency to become allergic to exposed particles and antigens. Normal individuals become tolerant to the same agents, instead of becoming allergic, a process that has yet to be understood.
"We found this tolerance is broken in the genetically-engineered transgenic mice, suggesting that the VEGF-induced break in tolerance contributes to the allergic sensitisation of asthmatic patients," Elias said.
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 150 million patients worldwide and 40 million in the US.
Asthma is a highly prevalent chronic disease estimated to cost at least $13 billion in the US alone each year. In the UK, there are four times as many people with asthma than with diabetes. The number of patients with asthma in the seven largest pharmaceutical markets is set to rise from 51.4 million in 2003 to 62.4 million in 2013, stimulating greater demand for cost-effective asthma therapies.
Datamonitor estimates that the market for asthma and chronic obstructive pulmonary disease (COPD) products will reach $18 billion by 2011.
The research appears in a report in the journal Nature Medicine.
