Tissue Factor Pathway Inhibitor Inhibits Endothelial Cell Proliferation via Association with the Very Low Density Lipoprotein Receptor
| Autor: | Dudley K. Strickland, Adonia E. Papathanassiu, Todd Hembrough, Jose F. Ruiz, Shawn J. Green |
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| Rok vydání: | 2001 |
| Předmět: |
Lipoproteins
VLDL receptor Very Low-Density Lipoprotein Receptor Biochemistry Antibodies Tissue factor pathway inhibitor medicine Humans Fibroblast Receptor Molecular Biology Cells Cultured biology Chemistry Cell Biology Cell biology Endothelial stem cell medicine.anatomical_structure Receptors LDL Coagulation biology.protein Endothelium Vascular Antibody Cell Division Protein Binding |
| Zdroj: | Journal of Biological Chemistry. 276:12241-12248 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m010395200 |
| Popis: | Tissue factor pathway inhibitor (TFPI) contains three Kunitz-type proteinase inhibitor domains and is a potent inhibitor of tissue factor-mediated coagulation. Here, we report that TFPI inhibits the proliferation of basic fibroblast growth factor-stimulated endothelial cells. A truncated form of TFPI, containing only the first two Kunitz-type proteinase inhibitor domains, has very little antiproliferative activity, suggesting that the carboxyl-terminal region of TFPI is responsible for this activity. Binding studies revealed that full-length TFPI, but not the truncated TFPI molecule, is recognized by the very low density lipoprotein receptor (VLDL receptor) indicating that this receptor is a novel high affinity endothelial cell receptor for TFPI. The antiproliferative activity of TFPI on endothelial cells is inhibited by the receptor-associated protein, a known antagonist of ligand binding by the VLDL receptor, and by anti-VLDL receptor antibodies. These results confirm that the antiproliferative activity of TFPI is mediated by the VLDL receptor and suggest that this receptor-ligand system may be a useful target for the development of new anti-angiogenic and antitumor agents. |
| Databáze: | OpenAIRE |
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