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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL090913-04
Application #
8211996
Study Section
Special Emphasis Panel (ZHL1-CSR-O (O1))
Program Officer
Tigno, Xenia
Project Start
2009-01-10
Project End
2013-12-31
Budget Start
2012-01-01
Budget End
2012-12-31
Support Year
4
Fiscal Year
2012
Total Cost
$136,350
Indirect Cost
$10,100
Name
University of California Davis
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618