Diabetic patients are at increased risk of morbidity mostly through the development of atherothrombotic vascular disease. Platelet hyperactivity and endothelial cell damage in type I diabetes suggest the hypothesis that in diabetes there is an increased potential for thrombus formation. To test this hypothesis and delineate the receptor(s)-ligand(s) participating, the investigators propose to use a recently developed analytical method based on real time confocal videomicroscopy. By using different immobilized ligands, such as von Willebrand Factor (vWF), fibrinogen, collagen type I, and subendothelial matrix, and by using various monoclonal antibodies that specifically block the functions of platelet glycoprotein (GP) Ib and integrin aIIbB3, and using a novel method based on fluorescent beads coated with GPIba recombinant fragment, the specific changes in receptor-ligand interactions in type I diabetes will be established. Secondly, they will probe the thrombogenicity of endothelial cells in diabetes using human umbilical vein endothelial cells (HUVEC) grown under elevated glucose levels. These endothelial cells, or their subendothelial matrices, will be placed in the flow chamber and thrombus formation over them be analyzed by real time confocal videomicroscopy under relevant flow conditions.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21HL065146-01
Application #
6053984
Study Section
Special Emphasis Panel (ZRG1-END (01))
Project Start
1999-09-30
Project End
2001-08-31
Budget Start
1999-09-30
Budget End
2000-08-31
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037