Abstract

Injury to vascular endothelium results in the rapid adhesion of platelets to the exposed underlying subendothelium, an important step in the processes of hemostasis and atherogenesis. This platelet adhesion requires the presence of von Willebrand factor, a multimeric plasma protein, which we have demonstrated also to be present within vascular subendothelium. We plan to identify the subendothelial binding vessel digestion studies, by examining the binding of VWF to purified known subendothelial substituents and by immuno-electron microscopic localization techniques. We also wish to determine whether there is a multimeric preferentiality in the binding of VWF to subendothelial constitutents. Elucidation of the binding of VWF to subendothelium would be an important advance in understanding the mechanism of platelet adhesion.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL032200-03
Application #
3343507
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1984-04-01
Project End
1989-03-31
Budget Start
1986-04-01
Budget End
1989-03-31
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Mount Sinai School of Medicine
Department
Type
Schools of Medicine
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10029

  Publications

Ross, J M; McIntire, L V; Moake, J L et al. (1998) Fibrillin containing elastic microfibrils support platelet adhesion under dynamic shear conditions. Thromb Haemost 79:155-61
Chow, T W; Turner, N A; Chintagumpala, M et al. (1998) Increased von Willebrand factor binding to platelets in single episode and recurrent types of thrombotic thrombocytopenic purpura. Am J Hematol 57:293-302
Rand, J H; Glanville, R W; Wu, X X et al. (1997) The significance of subendothelial von Willebrand factor. Thromb Haemost 78:445-50
Rand, J H; Wu, X X; Guller, S et al. (1997) Antiphospholipid immunoglobulin G antibodies reduce annexin-V levels on syncytiotrophoblast apical membranes and in culture media of placental villi. Am J Obstet Gynecol 177:918-23
Konstantopoulos, K; Chow, T W; Turner, N A et al. (1997) Shear stress-induced binding of von Willebrand factor to platelets. Biorheology 34:57-71
Rand, J H; Wu, X X; Andree, H A et al. (1997) Pregnancy loss in the antiphospholipid-antibody syndrome--a possible thrombogenic mechanism. N Engl J Med 337:154-60
Kamat, S G; Turner, N A; Konstantopoulos, K et al. (1997) Effects of Integrelin on platelet function in flow models of arterial thrombosis. J Cardiovasc Pharmacol 29:156-63
Wu, X X; Gordon, R E; Glanville, R W et al. (1996) Morphological relationships of von Willebrand factor, type VI collagen, and fibrillin in human vascular subendothelium. Am J Pathol 149:283-91
Ross, J M; McIntire, L V; Moake, J L et al. (1995) Platelet adhesion and aggregation on human type VI collagen surfaces under physiological flow conditions. Blood 85:1826-35
Zangari, M; Kaplan, K L; Glanville, R W et al. (1995) Reduced thrombogenicity of type VI collagen as compared to type I collagen. Thromb Res 79:429-36

Showing the most recent 10 out of 18 publications