Abstract

The SCOR in Thrombosis is designed to elucidate the role of von Willebrand factor, platelets and the vessel wall in arterial thrombosis. To accomplish this broad objective we have established a unique colony of pigs with homozygous von Willebrand's disease (VMD) that have undetectable levels of von Willebrand factor in plasma and platelets. These animals are resistant to coronary artery thrombosis but develop thrombosis when platelet VWF is restored. We plan to extend these studies to intracellular platelet messengers in order to determine the role of intraplatelet events in aggregation and release. We also will extend studies on platelet and smooth muscle cell (SMC) mitogens that induce SMC proliferation, the hallmark of the atherosclerotic lesion on which thrombosis usually occurs. Finally, we will focus on other vessel wall constituents, namely, thrombomodulin, endothelial cell and SMC transglutaminase, perturbations of which are of potential great importance in thrombosis. These studies will be supported by 3 cores: Administrative Core, Animal Core and a Clinical Core, the latter designed to take basic research observations and apply them to clinical situations. All SCOR projects are interrelated and the total contribution of the sum effort of these studies will be greater than any individual component.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Specialized Center (P50)
Project #
2P50HL026309-11
Application #
3106622
Study Section
Special Emphasis Panel (SRC (O1))
Project Start
1981-05-01
Project End
1996-04-30
Budget Start
1991-05-01
Budget End
1992-04-30
Support Year
11
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

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

  Publications

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
Ye, D; Nichols, T C; Dehmer, G J et al. (1997) Absence of human herpesvirus 8 genomes in coronary atherosclerosis in immunocompetent patients. Am J Cardiol 79:1245-7

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