Abstract

This is a revised renewal application to investigate the biochemistry and biology of human factor VII and tissue factor. The long term goals of the project are to acquire new information concerning factor VII structure-function relationships, the formation and regulation of factor VIIa-tissue factor activity in normal hemostasis, and the control of this activity in pathological coagulation and thrombosis. Specifically, the applicant proposes to: (1) investigate the functional role of O-glycosydically linked carbohydrate in the EGF- domain of factor VIII; (2) to determine the origin of fVIIa in blood; (3) to further elucidate the structural determinants in VII/VIIa required for binding to cell surface tissue factor; (4) to further characterize human TFPI-2 and investigate its role in hemostasis,(5) to study the mechanism of factor VII/VIIa clearance from the blood; and (6) to determine the dynamics of fVII/VIIa binding to cell-surface tissue factor.
Aims 4 and 5 are new to this revision, and one specific aim from the original application was deleted because that work is now complete and has been submitted for publication.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL035246-13
Application #
2713994
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1985-12-01
Project End
2000-05-31
Budget Start
1998-06-01
Budget End
2000-05-31
Support Year
13
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
University of New Mexico
Department
Pathology
Type
Schools of Medicine
DUNS #
829868723
City
Albuquerque
State
NM
Country
United States
Zip Code
87131

  Publications

Kamei, S; Kazama, Y; Kuijper, J L et al. (2001) Genomic structure and promoter activity of the human tissue factor pathway inhibitor-2 gene. Biochim Biophys Acta 1517:430-5
Arepally, G M; Kamei, S; Park, K S et al. (2000) Characterization of a murine monoclonal antibody that mimics heparin-induced thrombocytopenia antibodies. Blood 95:1533-40
Kazama, Y; Kamei, S; Kuijper, J L et al. (2000) Nucleotide sequence of the gene encoding murine tissue factor pathway inhibitor-2. Thromb Haemost 83:141-7
Neaud, V; Hisaka, T; Monvoisin, A et al. (2000) Paradoxical pro-invasive effect of the serine proteinase inhibitor tissue factor pathway inhibitor-2 on human hepatocellular carcinoma cells. J Biol Chem 275:35565-9
Kamei, S; Petersen, L C; Sprecher, C A et al. (1999) Inhibitory properties of human recombinant Arg24-->Gln type-2 tissue factor pathway inhibitor (R24Q TFPI-2). Thromb Res 94:147-52
Dahlen, J R; Foster, D C; Kisiel, W (1999) Inhibition of neutrophil elastase by recombinant human proteinase inhibitor 9. Biochim Biophys Acta 1451:233-41
Annand, R R; Dahlen, J R; Sprecher, C A et al. (1999) Caspase-1 (interleukin-1beta-converting enzyme) is inhibited by the human serpin analogue proteinase inhibitor 9. Biochem J 342 Pt 3:655-65
Bajaj, M S; Steer, S; Kuppuswamy, M N et al. (1999) Synthesis and expression of tissue factor pathway inhibitor by serum-stimulated fibroblasts, vascular smooth muscle cells and cardiac myocytes. Thromb Haemost 82:1663-72
Dahlen, J R; Jean, F; Thomas, G et al. (1998) Inhibition of soluble recombinant furin by human proteinase inhibitor 8. J Biol Chem 273:1851-4
Iino, M; Foster, D C; Kisiel, W (1998) Quantification and characterization of human endothelial cell-derived tissue factor pathway inhibitor-2. Arterioscler Thromb Vasc Biol 18:40-6

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