The goal of this SCORE renewal application is to identify and characterize key risk factors for thrombosis that will improve methods for its prevention and treatment. The SCOR is specifically designed to promote synergy between basic and clinical research. The SCOR is specifically designed to promote synergy between basic and clinical research. It includes randomized clinical trials to address optimal anticoagulant therapy for venous thrombosis (Project 1), biochemical projects that examine the membrane requirements for activated protein C function (Project 2), the structural requirements for the cofactor and signaling functions of the endothelial protein C receptor, the membrane requirements of the tissue factor/factor VIIa complex, and the use of gene-targeted mice to study the functions of vascular adhesion and signaling molecules in vivo. There is scientific overlap in the scientific goals of the laboratory-based projects. In addition, an essential link for all SCOR components is the Assay Core, which performs coagulation, ELISA, and DNA assays on blood samples from the patients in Project 1. The data from these assays will help answer mechanistic questions in the laboratory-oriented projects, which in turn, will help to define specific risk factors for thrombosis in the patients of Project 1. The SCOR is organized to facilitate generation and testing of hypotheses that will move between the basic and clinical arenas. The long-term objective is to better understand the etiology of thrombosis, thereby allowing design of better treatment strategies.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Specialized Center (P50)
Project #
5P50HL054502-08
Application #
6628981
Study Section
Special Emphasis Panel (ZHL1-CSR-F (S1))
Program Officer
Ganguly, Pankaj
Project Start
1996-03-01
Project End
2006-01-31
Budget Start
2003-03-01
Budget End
2004-01-31
Support Year
8
Fiscal Year
2003
Total Cost
$1,634,662
Indirect Cost
Name
Oklahoma Medical Research Foundation
Department
Type
DUNS #
077333797
City
Oklahoma City
State
OK
Country
United States
Zip Code
73104
Ireland, Helen A; Cooper, Jackie A; Drenos, Fotios et al. (2009) FVII, FVIIa, and downstream markers of extrinsic pathway activation differ by EPCR Ser219Gly variant in healthy men. Arterioscler Thromb Vasc Biol 29:1968-74
Looney, M R; Esmon, C T; Matthay, M A (2009) Role of coagulation pathways and treatment with activated protein C in hyperoxic lung injury. Thorax 64:114-20
Stowell, Sean R; Cho, Moonjae; Feasley, Christa L et al. (2009) Ligand reduces galectin-1 sensitivity to oxidative inactivation by enhancing dimer formation. J Biol Chem 284:4989-99
Miller, G J; Ireland, H A; Cooper, J A et al. (2008) Relationship between markers of activated coagulation, their correlation with inflammation, and association with coronary heart disease (NPHSII). J Thromb Haemost 6:259-67
Govers-Riemslag, J W P; Smid, M; Cooper, J A et al. (2007) The plasma kallikrein-kinin system and risk of cardiovascular disease in men. J Thromb Haemost 5:1896-903
Zheng, X; Li, W; Song, Y et al. (2007) Non-hematopoietic EPCR regulates the coagulation and inflammatory responses during endotoxemia. J Thromb Haemost 5:1394-400
Zheng, Xunzhen; Li, Weihong; Gu, Jian-Ming et al. (2007) Effects of membrane and soluble EPCR on the hemostatic balance and endotoxemia in mice. Blood 109:1003-9
Qu, D; Wang, Y; Esmon, N L et al. (2007) Regulated endothelial protein C receptor shedding is mediated by tumor necrosis factor-alpha converting enzyme/ADAM17. J Thromb Haemost 5:395-402
Kashiwagi, Aki; DiGirolamo, Carla M; Kanda, Yoshiaki et al. (2007) The postimplantation embryo differentially regulates endometrial gene expression and decidualization. Endocrinology 148:4173-84
Smith, Stephanie A; Mutch, Nicola J; Baskar, Deepak et al. (2006) Polyphosphate modulates blood coagulation and fibrinolysis. Proc Natl Acad Sci U S A 103:903-8

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