Platelet adhesion to the injured vessel wall plays a central role in the pathogenesis of thrombosis and atherosclerosis. Although von Willebrand's factor (vWF) has been shown to facilitate platelet adhesion to denuded vascular subendothelium, relatively little is known about the molecular mechanisms by which vWF binds to subendothelial components. In addition, because of the heterogeneity of vWF polymers, the number of functional domains for binding to subendothelium or platelet membrane receptors remains elusive. By utilizing a vWF oligomer of defined molecular weight which retains binding activity to platelets or to collagen, digest conditions will be established to produce fragments of vWF with platelet or collagen binding activity. Analysis of binding data and fragments obtained from digests of such a lower molecular weight oligomer will be relatively simplified. Lastly, the role of factor XIII in stabilization of vWF-dependent adhesion will be assessed. The ability of factor XIII to cross-link vWF to other plasma proteins such as fibrinogen, fibronectin, or subendothelial components will be analyzed using SDS polyacrylamide gel techniques. The site of factor XIII-dependent cross-linking on vWF will be isolated by selective proteolytic digestion of dansylcadaverine cross-linked to vWF. The information obtained from proteolytic digests of vWF oligomers will be compared to sites of factor XIII cross-linking activity on vWF to better understand the structural and functional relationships between platelets, vWF, and subendothelium.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
1K08HL001789-01
Application #
3082147
Study Section
Research Manpower Review Committee (MR)
Project Start
1985-07-01
Project End
1990-06-30
Budget Start
1985-07-01
Budget End
1986-09-14
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109