Bronchial asthma afflicts more than 5 percent of the U.S. population, and the incidence and prevalence are on the rise. A critical feature of the disease is structural changes in the wall of the airways (airway remodeling), which are correlated with morbidity. There is inadequate information describing the mechanisms of airway remodeling. Several key cells (epithelium, fibroblast, and smooth muscle cell) have been identified as critical players in the remodeling process. However, a study that addresses the interaction amongst these specific cells in response to injuries that mimic an asthmatic exacerbation has not been undertaken. Progress in our understanding is limited by a number of key factors including limited access to remodeled bronchial asthmatic tissue, inherent difficulty in characterizing a chronic response, and differentiating the complex interactions between multiple cells that are present simultaneously in vivo.
The specific aims of the project are to: 1) develop a novel tissue engineered model of the airway wall that consists of epithelial cells, fibroblasts, and smooth muscle cells in the normal anatomic and geometric arrangement, 2) utilize non-invasive optical techniques (two-photon microscopy) to quantify newly synthesized ECM proteins in live tissues, and 3) injure the tissue in a pattern which mimics asthma. Completion of the specific aims will provide answers to key questions related to airway remodeling, and bring us closer to not only halting but also reversing airway remodeling.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
7F32HL069646-02
Application #
6640722
Study Section
Special Emphasis Panel (ZRG1-SSS-3 (20))
Program Officer
Rothgeb, Ann E
Project Start
2002-01-01
Project End
Budget Start
2003-01-01
Budget End
2003-12-31
Support Year
2
Fiscal Year
2003
Total Cost
$40,986
Indirect Cost
Name
Duke University
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Miller, Cheryl; George, Steven; Niklason, Laura (2010) Developing a tissue-engineered model of the human bronchiole. J Tissue Eng Regen Med 4:619-27
Bergmark, Claes; Dewan, Asheesh; Orsoni, Alexina et al. (2008) A novel function of lipoprotein [a] as a preferential carrier of oxidized phospholipids in human plasma. J Lipid Res 49:2230-9
Tsimikas, Sotirios; Brilakis, Emmanouil S; Miller, Elizabeth R et al. (2005) Oxidized phospholipids, Lp(a) lipoprotein, and coronary artery disease. N Engl J Med 353:46-57