This research project will study the interrelationship among platelets, vessel wall, humoral coagulation factors and plasma proteinase inhibitors which are fundamental to the thrombotic process. The investigation of these interrelationships through a multifaceted, interdisciplinary approach will result in more effective prevention, diagnosis and treatment of thrombotic disease. Specific studies include the partial characterization of the platelet receptor for von Willebrand factor and the effect of von Willebrand factor on platelet-vessel wall interactions, the relationships between the platelet-active von Willebrand factor and the normal and injured vascular endothelial surface in the development of experimental atherosclerosis in swine, the relationships between lipoprotein metabolism and platelet function in the development of atherosclerosis, the definition of the mechanisms by which peptide growth factors stimulate replication in smooth muscle cells, the elucidation of the role of various intracellular messengers in the platelet function, the interaction of plasma proteinase inhibitors with thrombin, factor IXa and factor Xa, the examination of the molecular mechanism of action of heparin as an anticoagulant, physical biochemical studies of the interaction of fibrin with other components of plasma and a study of the interaction of fibronectin (cold-insoluble globulin) with fibrin. The project also contains a clinical core unit which will serve as a resource to the overall program in providing a mechanism for the facile """"""""translation"""""""" of basic science information into clinical treatment.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Specialized Center (P50)
Project #
5P50HL026309-08
Application #
3106626
Study Section
(SRC)
Project Start
1981-05-01
Project End
1991-04-30
Budget Start
1988-05-01
Budget End
1989-04-30
Support Year
8
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Fischer, Thomas H; Brittain, Julie; Trabalzini, Lorenza et al. (2003) The ras-binding domain of ral GDS-like protein-2 as a ras inhibitor in smooth muscle cells. Biochem Biophys Res Commun 305:934-40
Lai, T S; Hausladen, A; Slaughter, T F et al. (2001) Calcium regulates S-nitrosylation, denitrosylation, and activity of tissue transglutaminase. Biochemistry 40:4904-10
Blackwell, K L; Haroon, Z A; Shan, S et al. (2000) Tamoxifen inhibits angiogenesis in estrogen receptor-negative animal models. Clin Cancer Res 6:4359-64
Haroon, Z A; Raleigh, J A; Greenberg, C S et al. (2000) Early wound healing exhibits cytokine surge without evidence of hypoxia. Ann Surg 231:137-47
Haroon, Z A; Lai, T S; Hettasch, J M et al. (1999) Tissue transglutaminase is expressed as a host response to tumor invasion and inhibits tumor growth. Lab Invest 79:1679-86
Dehmer, G J; Nichols, T C; Li, S et al. (1999) Effects of an ionic and nonionic contrast agent on von Willebrand factor assessed during coronary angiography. Am J Cardiol 84:223-5, A8
Haroon, Z A; Hettasch, J M; Lai, T S et al. (1999) Tissue transglutaminase is expressed, active, and directly involved in rat dermal wound healing and angiogenesis. FASEB J 13:1787-95
White 2nd, G C; Fischer, T H; Duffy, C M (1998) Rap1b association with the platelet cytoskeleton occurs in the absence of glycoproteins IIb/IIIa. Thromb Haemost 79:832-6
Nichols, T C; Bellinger, D A; Reddick, R L et al. (1998) von Willebrand factor does not influence atherogenesis in arteries subjected to altered shear stress. Arterioscler Thromb Vasc Biol 18:323-30
Hettasch, J M; Peoples, K A; Greenberg, C S (1997) Analysis of factor XIII substrate specificity using recombinant human factor XIII and tissue transglutaminase chimeras. J Biol Chem 272:25149-56

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