scholarly journals Vascular Gas6 contributes to thrombogenesis and promotes tissue factor up-regulation after vessel injury in mice

Blood ◽  
2013 ◽  
Vol 121 (4) ◽  
pp. 692-699 ◽  
Author(s):  
Richard S. Robins ◽  
Catherine A. Lemarié ◽  
Sandrine Laurance ◽  
Meghedi N. Aghourian ◽  
Jianqiu Wu ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Thrombus Formation ◽  
Vascular Wall ◽  
Specific Gene ◽  
Tissue Factor Expression ◽  
Vessel Injury ◽  
Factor Expression ◽  
Platelet Signaling

Abstract Gas6 (growth-arrest specific gene 6) plays a role in thrombus stabilization. Gas6 null (−/−) mice are protected from lethal venous and arterial thromboembolism through platelet signaling defects induced only by 5μM ADP and 10μM of the thromboxane analog, U46619. This subtle platelet defect, despite a dramatic clinical phenotype, raises the possibility that Gas6 from a source other than platelets contributes to thrombus formation. Thus, we hypothesize that Gas6 derived from the vascular wall plays a role in venous thrombus formation. Bone marrow transplantation and platelet depletion/reconstitution experiments generating mice with selective ablations of Gas6 from either the hematopoietic or nonhematopoietic compartments demonstrate an approximately equal contribution by Gas6 from both compartments to thrombus formation. Tissue factor expression was significantly reduced in the vascular wall of Gas6−/− mice compared with WT. In vitro, thrombin-induced tissue factor expression was reduced in Gas6−/− endothelial cells compared with wild-type endothelium. Taken together, these results demonstrate that vascular Gas6 contributes to thrombus formation in vivo and can be explained by the ability of Gas6 to promote tissue factor expression and activity. These findings support the notion that vascular wall-derived Gas6 may play a pathophysiologic role in venous thromboembolism.

Macrovascular thrombosis is driven by tissue factor derived primarily from the blood vessel wall

Blood ◽  
2005 ◽  
Vol 105 (1) ◽  
pp. 192-198 ◽  
Author(s):  
Sharlene M. Day ◽  
Jennifer L. Reeve ◽  
Brian Pedersen ◽  
Diana M Farris ◽  
Daniel D. Myers ◽  
...  
Keyword(s):  
Blood Vessel ◽  
Tissue Factor ◽  
Vessel Wall ◽  
Thrombus Formation ◽  
Vena Cava ◽  
Vascular Wall ◽  
Blood Vessel Wall ◽  
Wild Type

Abstract Leukocytes and leukocyte-derived microparticles contain low levels of tissue factor (TF) and incorporate into forming thrombi. Although this circulating pool of TF has been proposed to play a key role in thrombosis, its functional significance relative to that of vascular wall TF is poorly defined. We tested the hypothesis that leukocyte-derived TF contributes to thrombus formation in vivo. Compared to wild-type mice, mice with severe TF deficiency (ie, TF–/–, hTF-Tg+, or “low-TF”) demonstrated markedly impaired thrombus formation after carotid artery injury or inferior vena cava ligation. A bone marrow transplantation strategy was used to modulate levels of leukocyte-derived TF. Transplantation of low-TF marrow into wild-type mice did not suppress arterial or venous thrombus formation. Similarly, transplantation of wild-type marrow into low-TF mice did not accelerate thrombosis. In vitro analyses revealed that TF activity in the blood was very low and was markedly exceeded by that present in the vessel wall. Therefore, our results suggest that thrombus formation in the arterial and venous macrovasculature is driven primarily by TF derived from the blood vessel wall as opposed to leukocytes.

ENDOTHELIAL GAS6 Contributes to Thrombogenesis and Promotes TISSUE FACTOR Upregulation DURING Vessel Injury

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 702-702
Author(s):  
Richard Robins ◽  
Catherine A Lemarie ◽  
Jianqiu Wu ◽  
Mark Blostein
Keyword(s):  
Tissue Factor ◽  
Conflicts Of Interest ◽  
Thrombus Formation ◽  
Vena Cava ◽  
Functional Assay ◽  
Mrna Induction ◽  
Vessel Injury ◽  
Platelet Depletion

Abstract Abstract 702 Gas6 is a vitamin K-dependent, secreted protein that amplifies platelet aggregation and secretion in response to platelet agonists. Gas6−/− mice are protected from experimentally induced lethal venous and arterial thromboembolism. This protection has been attributed to defective aggregation in platelets from gas6−/− mice. However, this platelet phenotype was only observed when platelets were challenged by only one agonist, ADP, and only at a concentrations of 5.0μM. This subtle platelet abnormality resulting in a rather dramatic clinical phenotype raise the possibility that gas6 from a source other than platelets contributes to thrombus formation. We hypothesize that gas6 derived from the endothelium plays a role in venous thrombus formation. Gas6−/− mice are protected against venous thrombosis induced by 0.37 M FeCl3 in the inferior vena cava (IVC). Bone marrow transplantation experiments generating mice with selective ablations of gas6 from either the hematopoietic or non-hematopoietic compartments demonstrate an approximately equal contribution by gas6 from both compartments to thrombus formation. Platelet depletion in wild type or gas6−/− mice followed by reconstitution with platelets from either WT or gas6−/− mice confirm that gas6 from compartments other than the platelet contribute to thrombosis development. Furthermore, gas6−/− mice are hyporesponsive to FeCl3 mediated tissue factor induction in venous endothelium, as observed by immunofluorescence staining and later validated by a functional assay. In addition, in vitro, gas6−/− endothelial cells are hyporesponsive to thrombin mediated tissue factor mRNA induction. Taken together, these results suggest that non-hematopoietic gas6, possibly from the endothelium, contributes to thrombus formation in vivo and can be explained by the ability of gas6 to promote endothelial tissue factor induction. These findings support the notion that endothelial gas6 may play a pathophysiologic role in venous thromboembolism. Disclosures: No relevant conflicts of interest to declare.

Upregulation of tissue factor expression by avastin: ex vivo and in vitro data

2012 ◽  
Vol 129 ◽  
pp. S170
Author(s):  
E. Napoleone ◽  
A. Cutrone ◽  
D. Cugino ◽  
R. Tambaro ◽  
A. De Curtis ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Ex Vivo ◽  
Tissue Factor Expression ◽  
Factor Expression ◽  
Vitro Data ◽  
In Vitro Data

Nutritional compounds influence tissue factor expression and inflammation of chronic kidney disease patients in vitro

Nutrition ◽  
2011 ◽  
Vol 27 (9) ◽  
pp. 967-972 ◽  
Author(s):  
Cecilia M. Shing ◽  
Murray J. Adams ◽  
Robert G. Fassett ◽  
Jeff S. Coombes
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Tissue Factor ◽  
Tissue Factor Expression ◽  
Factor Expression ◽  
Nutritional Compounds

scholarly journals Dietary α-Linolenic Acid Inhibits Arterial Thrombus Formation, Tissue Factor Expression, and Platelet Activation

2011 ◽  
Vol 31 (8) ◽  
pp. 1772-1780 ◽  
Author(s):  
Erik W. Holy ◽  
Marc Forestier ◽  
Eva K. Richter ◽  
Alexander Akhmedov ◽  
Florian Leiber ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Linolenic Acid ◽  
Platelet Activation ◽  
Thrombus Formation ◽  
Tissue Factor Expression ◽  
Arterial Thrombus ◽  
Factor Expression

scholarly journals Increased tissue factor expression on circulating monocytes in chronic HIV infection: relationship to in vivo coagulation and immune activation

Blood ◽  
2010 ◽  
Vol 115 (2) ◽  
pp. 161-167 ◽  
Author(s):  
Nicholas T. Funderburg ◽  
Elizabeth Mayne ◽  
Scott F. Sieg ◽  
Robert Asaad ◽  
Wei Jiang ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Tissue Factor ◽  
Immune Activation ◽  
Interleukin 6 ◽  
Plasma Levels ◽  
Thrombus Formation ◽  
Hiv Replication ◽  
Increased Risk

Abstract HIV infection is associated with an increased risk of thrombosis; and as antiretroviral therapy has increased the lifespan of HIV-infected patients, their risk for cardiovascular events is expected to increase. A large clinical study found recently that all-cause mortality for HIV+ patients was related to plasma levels of interleukin-6 and to D-dimer products of fibrinolysis. We provide evidence that this elevated risk for coagulation may be related to increased proportions of monocytes expressing cell surface tissue factor (TF, thromboplastin) in persons with HIV infection. Monocyte TF expression could be induced in vitro by lipopolysaccharide and flagellin, but not by interleukin-6. Monocyte expression of TF was correlated with HIV levels in plasma, with indices of immune activation, and with plasma levels of soluble CD14, a marker of in vivo lipopolysaccharide exposure. TF levels also correlated with plasma levels of D-dimers, reflective of in vivo clot formation and fibrinolysis. Thus, drivers of immune activation in HIV disease, such as HIV replication, and potentially, microbial translocation, may activate clotting cascades and contribute to thrombus formation and cardiovascular morbidities in HIV infection.

Abstract 14366: T-lymphocytes May Contribute to Thrombus Formation in Patients With Acute Coronary Syndrome via Expression of Tissue Factor

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Giovanni Cimmino ◽  
Giovanni Ciccarelli ◽  
Stefano Conte ◽  
Grazia Pellegrino ◽  
Luigi Insabato ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Tissue Factor ◽  
Thrombus Formation ◽  
Specific Antigen ◽  
Activated T Cells ◽  
Coronary Syndrome ◽  
Stable Cad

Background: Activation of T-cells plays an important role in the pathophysiology of acute coronary syndromes (ACS). We have previously shown that plaques from ACS patients are characterized by a selective oligoclonal expansion of T-cells, indicating a specific, antigen-mediated recruitment of T-cells within the unstable lesions. We have also previously reported that activated T-cells in vitro express functional Tissue Factor (TF) on their surface. At the moment, however it is not known whether expression of TF by T-cells may contribute to thrombus formation in vivo. Methods: Blood was collected from the aorta and the coronary sinus of 13 NSTEMI and 10 stable CAD patients. CD3+ cells were selectively isolated and TF gene expression (real time PCR)and protein levels (western blot) were evaluated. In additional 7 STEMI patients, thrombotic formation material was obtained from the occluded coronary artery by catheter aspiration during primary PCI. TF expression in CD3+ cells was evaluated by immunohistochemistry and confocal microscopy. Results: Transcardiac TF expression in CD3+ cells was significantly higher in NSTEMI patients as compared to CD3+ cells obtained from stable CAD patients. Interestingly, thrombi aspirated from STEMI patients resulted enriched in CD3+cells, which expressed TF on their surface as shown in the figure. Conclusions: Our data demonstrate that in patients with ACS, T-lymphocytes may express surface TF, thus contributing to the process of thrombus formation. This finding may shed new light into the pathophysiologyof ACS.

Sign in / Sign up

Export Citation Format

Share Document