ID: 098 Adenovirus Mediated Expression of Tissue Factor Pathway Inhibitor-2 Inhibits Endothelial Cell Migration and Angiogenesis

2006 ◽  
Vol 4 (s1) ◽  
pp. 68-68
Author(s):  
L. Ivanciu ◽  
R. Gerard ◽  
H. Tang ◽  
C. Lupu ◽  
F. Lupu
Keyword(s):  
Cell Migration ◽  
Endothelial Cell ◽  
Tissue Factor ◽  
Tissue Factor Pathway Inhibitor ◽  
Endothelial Cell Migration ◽  
Tissue Factor Pathway

Tissue factor pathway inhibitor (TFPI) interferes with endothelial cell migration by inhibition of both the Erk pathway and focal adhesion proteins

2008 ◽  
Vol 99 (03) ◽  
pp. 576-585 ◽  
Author(s):  
Mathieu Provençal ◽  
Marisol Michaud ◽  
Édith Beaulieu ◽  
David Ratel ◽  
Georges-Étienne Rivard ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Migration ◽  
Endothelial Cell ◽  
Tissue Factor ◽  
Focal Adhesion ◽  
Tissue Factor Pathway Inhibitor ◽  
Endothelial Cell Migration ◽  
Cell Functions ◽  
Tissue Factor Pathway

SummaryTissue factor pathway inhibitor (TFPI) is a plasma Kunitz-type serine protease inhibitor that is mainly known for its inhibition of tissue factor-mediated coagulation. In addition to its anticoagulant properties, emerging data show that TFPI may also regulate endothelial cell functions via a non-haemostatic pathway. In this work we demonstrate that at concentrations within the physiological range,TFPI inhibits both endothelial cell migration and their differentiation into capillary-like structures in vitro. These effects were specific to endothelial cells since no inhibitory effect was observed on the migration of tumor (glio- blastoma) cells. Inhibition of endothelial cell migration was correlated with a concomitant loss in cell adhesion,suggesting an alteration of focal adhesion complex integrity. Accordingly,we observed thatTFPI inhibited the phosphorylation of focal adhesion kinase and paxillin,two key proteins involved in the scaffolding of these complexes, and that this effect was specific to endothelial cells. These results suggest that TFPI influences the angiogenic process via a non-haemostatic pathway, by downregulating the migratory mechanisms of endothelial cells.

Decreased Plasma Tissue Factor Pathway Inhibitor Levels in Patients with Thrombotic Thrombocytopenic Purpura

1995 ◽  
Vol 73 (01) ◽  
pp. 010-014 ◽  
Author(s):  
Hideo Wada ◽  
Masayuki Kobayashi ◽  
Yoshihiro Wakita ◽  
Minori Shimura ◽  
Tutomu Nakase ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Healthy Volunteers ◽  
Tissue Factor ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Plasma Levels ◽  
Tissue Factor Pathway Inhibitor ◽  
Vascular Endothelial Cell ◽  
Vascular Endothelial ◽  
Thrombocytopenic Purpura ◽  
Tissue Factor Pathway

SummaryWe measured plasma levels of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in patients with thrombotic thrombocytopenic purpura (TTP) and disseminated intravascular coagulation (DIC) to examine the relationship between TFPI and vascular endothelial cell injury. TF antigen was detected in the plasma of healthy volunteers, and the levels were significantly increased in the patients with DIC, but decreased slightly in those with TTP. Plasma TFPI levels were significantly decreased in patients with TTP compared with those in healthy volunteers. The concentration of plasma thrombomodulin (TM) antigen was significantly higher in those with TTP than in normal volunteers. One month after treatment, TTP patients showed a significant decrease in plasma TM levels, and a significant increase, in plasma TFPI levels, but plasma levels of TF antigen were not significantly increased. As plasma TFPI/TF ratio was significantly increased after treatment, the hypercoagulable state was therefore improved after treatment. There was no significant difference in plasma TF and TFPI levels between those who achieved complete remission (CR) and those who died. However, plasma TM levels were significantly higher in those who died than in those who achieved CR. Plasma TFPI levels might reflect injury of vascular endothelial cells as do plasma TM levels, and decreased plasma TFPI/TF ratio and vascular endothelial cell injuries might play causative roles in TTP.

scholarly journals Endothelial-derived tissue factor pathway inhibitor regulates arterial thrombosis but is not required for development or hemostasis

Blood ◽  
2010 ◽  
Vol 116 (10) ◽  
pp. 1787-1794 ◽  
Author(s):  
Thomas A. White ◽  
Tucker Johnson ◽  
Natalia Zarzhevsky ◽  
Cindy Tom ◽  
Sinny Delacroix ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Surface ◽  
Tissue Factor ◽  
Knockout Mice ◽  
Arterial Thrombosis ◽  
Tissue Factor Pathway Inhibitor ◽  
Conditional Knockout ◽  
Endothelial Cell Surface ◽  
Tissue Factor Pathway ◽  
Exon 4

AbstractThe antithrombotic surface of endothelium is regulated in a coordinated manner. Tissue factor pathway inhibitor (TFPI) localized at the endothelial cell surface regulates the production of FXa by inhibiting the TF/VIIa complex. Systemic homozygotic deletion of the first Kunitz (K1) domain of TFPI results in intrauterine lethality in mice. Here we define the cellular sources of TFPI and their role in development, hemostasis, and thrombosis using TFPI conditional knockout mice. We used a Cre-lox strategy and generated mice with a floxed exon 4 (TFPIFlox) which encodes for the TFPI-K1 domain. Mice bred into Tie2-Cre and LysM-Cre lines to delete TFPI-K1 in endothelial (TFPITie2) and myelomonocytic (TFPILysM) cells resulted in viable and fertile offspring. Plasma TFPI activity was reduced in the TFPITie2 (71% ± 0.9%, P < .001) and TFPILysM (19% ± 0.6%, P < .001) compared with TFPIFlox littermate controls. Tail and cuticle bleeding were unaffected. However, TFPITie2 mice but not TFPILysM mice had increased ferric chloride–induced arterial thrombosis. Taken together, the data reveal distinct roles for endothelial- and myelomonocytic-derived TFPI.

Endothelial cell-anchored tissue factor pathway inhibitor regulates tumor metastasis to the lung in mice

2015 ◽  
Vol 55 (5) ◽  
pp. 882-896 ◽  
Author(s):  
Jiping Wang ◽  
Jiajun Xiao ◽  
Danping Wen ◽  
Xie Wu ◽  
Zuohua Mao ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Tissue Factor ◽  
Tumor Metastasis ◽  
Tissue Factor Pathway Inhibitor ◽  
Tissue Factor Pathway

Cortactin activation by FVIIa/tissue factor and PAR2 promotes endothelial cell migration

2011 ◽  
Vol 300 (3) ◽  
pp. R577-R585 ◽  
Author(s):  
Tang Zhu ◽  
Joseph A. Mancini ◽  
Przemyslaw Sapieha ◽  
Chun Yang ◽  
Jean-Sébastien Joyal ◽  
...  
Keyword(s):  
Cell Migration ◽  
Endothelial Cell ◽  
Tissue Factor ◽  
Actin Polymerization ◽  
Coagulation Factors ◽  
Cellular Migration ◽  
Endothelial Cell Migration ◽  
Factor Vii ◽  
Cell Periphery ◽  
Migration Assay

Cellular migration is a complex process that requires the polymerization of actin filaments to drive cellular extension. Smooth muscle and cancer cell migration has been shown to be affected by coagulation factors, notably the factor VII (FVIIa) and tissue factor (TF) complex. The present studies delineated mediators involved with the process of FVIIa/TF-induced cell migration and utilized a simple, precise, and reproducible, migration assay. Both FVIIa and protease-activated receptor-2 (PAR2)-activating peptide, SLIGRL, increased the migration rate of porcine cerebral microvascular endothelial cells (pCMVECs) overexpressing human TF. Ras homolog gene family member A (RhoA) and cortactin were upregulated during the process; expression of HIF, actin polymerization nuclear diaphanous-related formin-1 and -2 (Dia1, and Dia2) were unaffected. Gene silencing by shRNA to PAR2, RhoA, and cortactin attenuated this gene upregulation and migration induced by FVIIa/TF. Utilizing immunocellular localization, we demonstrate that during FVIIa/TF and PAR2 activation, cortactin molecules translocate from the cytoplasm to the cell periphery and assist in lamellipodia formation of pCMVECs. Overall, we demonstrate a novel regulation and role for cortactin in FVIIa/TF-mediated endothelial cell migration that occurs through a PAR2 and RhoA dependent mechanism.

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