Chronic Asthma is a disease on the rise with considerable associated morbidity. The pathology most often linked with asthma is airway remodeling. When the conducting airway becomes remodeled changes occur in the epithelium, extracellular matrix, smooth muscle and vascular compartment. The mechanism that drives vascular remodeling in asthma is not completely understood, using archived tissue from an established nonhuman primate model of chronic asthma this grant proposes the following Specific Aims: 1) To establish the epithelium as the main source of vascular growth factors (VEGF) in chronic asthma and 2) to establish the mechanism that vascular growth factor message and expression are increased in airway epithelial cells. To accomplish these aims we will use immunohistochemistry, in situ hybridization, laser capture microdissection along with quantitative stereology to establish that increased epithelial derived VEGF is spatially concentrated in areas of increase vascular density and is the most abundant source of VEGF. The mechanism of increased VEGF message and expression will be established using a promoter reporter construct in airway epithelial cells. The significance of this research is that it will establish the central role the epithelium plays in the process of airway remodeling and the mechanism of action. This research will translate into more specific, individualized therapy for patients who suffer from asthma and related chronic lung disease.
Patient with chronic asthma have symptoms because their airways have been altered by ongoing inflammation. One of the changes seen is an increase in blood vessel density in the airway wall. This research grant will explore to ways these vascular changes occur and hopefully identify a potential target for therapy.
|Avdalovic, Mark V; Tyler, Nancy K; Putney, Lei et al. (2012) Ozone exposure during the early postnatal period alters the timing and pattern of alveolar growth and development in nonhuman primates. Anat Rec (Hoboken) 295:1707-16|