The influence of exogenous tissue factor on the regulators of proliferation and apoptosis in endothelial cells.
BACKGROUND
The exposure of tissue factor (TF) at the site of injury or trauma is a rapid process that leads to the initiation of blood coagulation as well as homeostatic processes giving rise to vascular repair.


OBJECTIVE
By exposing human endothelial cells to combinations of exogenous TF and factor VIIa (FVIIa) in serum-free medium, the influence of TF concentrations on cellular proliferation and apoptosis was investigated.


RESULTS
Lower concentrations of TF resulted in increased cellular proliferation as well as upregulation of cyclin D1, downregulation of p21 and p27 and induction of tube formation in vitro. Conversely, incubation with higher concentrations of TF resulted in the activation of caspase-3, expression of p53 and Bax, translocation of p53 into the nucleus and induction of DNA fragmentation. Incubation of the cells with TF/FVIIa led to a lower proliferation rate with additional upregulation in p27.


CONCLUSIONS
TF seems to have a bifunctional role in determining the fate of endothelial cells, depending on the concentration and the interactions of this protein. The release of TF in the locality of the injured tissue makes this protein an ideal factor for ascertaining the level of injury and determining the fate of the cells.
Pradier
Amandine
A
Biomedical Section, Department of Biological Sciences, University of Hull, Hull, UK.
Ettelaie
Camille
C
D021581:Active Transport, Cell Nucleus; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape; D002478:Cells, Cultured; D056741:Cyclin D; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000378:metabolism; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004789:Enzyme Activation; D015942:Factor VIIa / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism* / Q000494:pharmacology; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494826:BAX protein, human; C493956:CDKN1A protein, human; C436291:CDKN1B protein, human; D056741:Cyclin D; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D050760:Cyclin-Dependent Kinase Inhibitor p27; D013925:Thromboplastin; D015942:Factor VIIa; D053148:Caspase 3