Chicken embryos which undergo ablation f cardiac neural crest manifest characteristic heart defects. This stud will test the hypothesis that the elastic arteries in these embryos will also have an associated defect, in the following parameters: (1) the composition, deployment and alignment of the elastic matrix of the vessels; (2) the function of the vessels; and (3) the ability of the vessels to respond to stimulation of elastogenesis. These hypotheses will be tested by integrated analyses of structure and function in control and experimental embryos ranging from stage 28 (septation) to stage 46(hatching). The time of occurrence and distribution of tropoelastins and other elastinrelated proteins will be determined by immunohistochemistry. The alignment of the elastic matrix will be determined by measurement of induced birefringence. Functional capacity of the vessels will be determined by measurement of their active and passive length=tension relationships. Response to elastogenic stimulation will be measured in vessels in vitro. This integrated study of structure, function and experimental embryology will establish the basic biology of normal vessel development; and abnormal vessel development that accompanies heart anomalies. These data may then provide a basis for rational design of a prognosis and treatment plan for the pulmonary artery defect that accompanies cyanotic congenital heart disease in man; which may be fatal; and for which there is n cure.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL042164-06
Application #
2220322
Study Section
Special Emphasis Panel (SRC (04))
Project Start
1988-09-30
Project End
1994-07-31
Budget Start
1992-08-01
Budget End
1994-07-31
Support Year
6
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Nebraska Medical Center
Department
Genetics
Type
Schools of Medicine
DUNS #
City
Omaha
State
NE
Country
United States
Zip Code
68198