Abstract

The long-term goal of this laboratory is to employ cell culture to delineate the interactions between vascular endothelial cells and blood-molecular systems, both in health and disease. The more immediate objective of this work, and that to which this proposal is specifically addressed, is to develop an understanding of endothelial cell-mediated fibrinolysis as an approach for investigating the role of the endothelium in thrombolysis. Rabbit and borine vascular endothelial cells cultured in vitro will be employed to characterize the nature of signals which influence the synthesis, secretion, and activity of a recently described cellular plasminogen activator and fibrinolytic inhibitor.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL022289-08
Application #
3336817
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1978-07-01
Project End
1986-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
8
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Scripps Research Institute
Department
Type
DUNS #
City
San Diego
State
CA
Country
United States
Zip Code
92037

  Publications

Keeton, M; Eguchi, Y; Sawdey, M et al. (1993) Cellular localization of type 1 plasminogen activator inhibitor messenger RNA and protein in murine renal tissue. Am J Pathol 142:59-70
Schneiderman, J; Sawdey, M S; Keeton, M R et al. (1992) Increased type 1 plasminogen activator inhibitor gene expression in atherosclerotic human arteries. Proc Natl Acad Sci U S A 89:6998-7002
Seiffert, D; Keeton, M; Eguchi, Y et al. (1991) Detection of vitronectin mRNA in tissues and cells of the mouse. Proc Natl Acad Sci U S A 88:9402-6
Sawdey, M S; Loskutoff, D J (1991) Regulation of murine type 1 plasminogen activator inhibitor gene expression in vivo. Tissue specificity and induction by lipopolysaccharide, tumor necrosis factor-alpha, and transforming growth factor-beta. J Clin Invest 88:1346-53
Schleef, R R; Loskutoff, D J; Podor, T J (1991) Immunoelectron microscopic localization of type 1 plasminogen activator inhibitor on the surface of activated endothelial cells. J Cell Biol 113:1413-23
Sane, D C; Moser, T L; Parker, C J et al. (1990) Highly sulfated glycosaminoglycans augment the cross-linking of vitronectin by guinea pig liver transglutaminase. Functional studies of the cross-linked vitronectin multimers. J Biol Chem 265:3543-8
Schleef, R R; Podor, T J; Dunne, E et al. (1990) The majority of type 1 plasminogen activator inhibitor associated with cultured human endothelial cells is located under the cells and is accessible to solution-phase tissue-type plasminogen activator. J Cell Biol 110:155-63
Campochiaro, P A; Mimuro, J; Sugg, R et al. (1989) Retinal pigment epithelial cells produce a latent fibrinolytic inhibitor that is antigenically and biochemically related to type 1 plasminogen activator inhibitor produced by vascular endothelial cells. Exp Eye Res 49:195-203
Mimuro, J; Loskutoff, D J (1989) Binding of type 1 plasminogen activator inhibitor to the extracellular matrix of cultured bovine endothelial cells. J Biol Chem 264:5058-63
Mimuro, J; Loskutoff, D J (1989) Purification of a protein from bovine plasma that binds to type 1 plasminogen activator inhibitor and prevents its interaction with extracellular matrix. Evidence that the protein is vitronectin. J Biol Chem 264:936-9

Showing the most recent 10 out of 23 publications