LIM-only protein FHL2 attenuates vascular tissue factor activity, inhibits thrombus formation in mice and FHL2 genetic variation associates with human venous thrombosis

Previously, we showed that cells derived from nonvascular tissues initiate clotting primarily by markedly increasing the activity of coagulation factor VII. Cells derived from vascular tissue do not normally exhibit this property (tissue factor activity). In this study, we have characterized the relationship between the tissue factor activity of cultured cells derived from normal tissues and the number of receptors they possess for coagulation factor VII. Only cultured nonvascular cells expressed tissue factor activity or possessed receptors for 125I-factor VII. Fetal lung cells, the nonvascular tissue with the largest amount of procoagulant and tissue factor activity, possessed the most receptors for 125I-factor VII (880,000/cell). Bovine corneal endothelial cells, the nonvascular tissue possessing the fewest number of receptors (2,400/cell), had the least amount of procoagulant or tissue factor activity. The affinity of nonvascular cells for 125I- factor VII varied for the cells studied (Kd congruent to 1.3–90 X 10(- 10) M). Vascular cells expressed no tissue factor activity, nor did they bind 125I-factor VII. 125I-factor VII and unlabeled factor VII bound to cells had identical procoagulant activities. These results indicate that the ability of cultured cells to initiate coagulation may be regulated in part by the number of receptors they possess for factor VII.

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Increased monocyte tissue factor activity in women following cerebral venous thrombosis

Journal of Neurology ◽

10.1007/s00415-003-1060-x ◽

2003 ◽

Vol 250 (5) ◽

pp. 631-632 ◽

Cited By ~ 2

Author(s):

Hans H�lschermann ◽

Werner Haberbosch ◽

Helma-Meta Terhalle ◽

Behnoush Parviz ◽

J�rg Kraus ◽

...

Keyword(s):

Venous Thrombosis ◽

Tissue Factor ◽

Cerebral Venous Thrombosis ◽

Factor Activity ◽

Tissue Factor Activity

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The number of receptors for factor VII correlates with the ability of cultured cells to initiate coagulation

Blood ◽

10.1182/blood.v63.2.434.434 ◽

1984 ◽

Vol 63 (2) ◽

pp. 434-438 ◽

Cited By ~ 29

Author(s):

GM Rodgers ◽

GJ Jr Broze ◽

MA Shuman

Keyword(s):

Tissue Factor ◽

Vascular Tissue ◽

Cultured Cells ◽

Coagulation Factor ◽

Fetal Lung ◽

Factor Vii ◽

Factor Activity ◽

Coagulation Factor Vii ◽

Normal Tissues ◽

Tissue Factor Activity

Abstract Previously, we showed that cells derived from nonvascular tissues initiate clotting primarily by markedly increasing the activity of coagulation factor VII. Cells derived from vascular tissue do not normally exhibit this property (tissue factor activity). In this study, we have characterized the relationship between the tissue factor activity of cultured cells derived from normal tissues and the number of receptors they possess for coagulation factor VII. Only cultured nonvascular cells expressed tissue factor activity or possessed receptors for 125I-factor VII. Fetal lung cells, the nonvascular tissue with the largest amount of procoagulant and tissue factor activity, possessed the most receptors for 125I-factor VII (880,000/cell). Bovine corneal endothelial cells, the nonvascular tissue possessing the fewest number of receptors (2,400/cell), had the least amount of procoagulant or tissue factor activity. The affinity of nonvascular cells for 125I- factor VII varied for the cells studied (Kd congruent to 1.3–90 X 10(- 10) M). Vascular cells expressed no tissue factor activity, nor did they bind 125I-factor VII. 125I-factor VII and unlabeled factor VII bound to cells had identical procoagulant activities. These results indicate that the ability of cultured cells to initiate coagulation may be regulated in part by the number of receptors they possess for factor VII.

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Abstract 3741: Stress Promotes Arterial Thrombosis through Activation of the Sympathetic Nervous System

Circulation ◽

10.1161/circ.118.suppl_18.s_478-c ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Simon F Stampfli ◽

Giovanni G Camici ◽

Irene Garcia ◽

Thomas F Luscher ◽

Felix C Tanner

Keyword(s):

Nervous System ◽

Sympathetic Nervous System ◽

Tissue Factor ◽

Arterial Thrombosis ◽

Cardiovascular Events ◽

Bleeding Time ◽

Thrombus Formation ◽

Factor Activity ◽

Tissue Factor Activity ◽

Sympathetic Nervous

Background: Several lines of evidence demonstrate a correlation between stress and cardiovascular mortality and morbidity. Myocardial infarction can be triggered by life threatening events such as earthquakes or missile attacks, and even every day stressful situations such as anger were shown to correlate with adverse cardiovascular events, primarily caused by arterial thrombus formation. The sympathetic nervous system is known to mediate various stress-related effects; however, a mechanism linking stress and thrombosis has not been described. Methods: To investigate the influence of acute stress on arterial thrombosis, mice were subjected to a restraint stress protocol for 20 hours. Subsequently, arterial thrombosis was induced by photochemical injury in vivo . Furthermore, coagulation times (PT, aPTT) and tissue factor activity were assayed in plasma and carotid artery, respectively. In addition, tail bleeding time was assessed. To investigate the role of the sympathetic nervous system, chemical sympathectomy was performed by treating mice with 6-Hydroxydopamine (OHDA) or control vehicle, respectively. Results: Time to thrombotic occlusion was significantly decreased in stressed mice as compared to controls (−26.7 ± 4.0 minutes, p<0.001, n=5). In sympathectomized mice stress failed to decrease time to occlusion (−8.1 ± 5.6 minutes, n.s., n=5); Sympathectomy alone had no effect on time to occlusion as compared to vehicle treatment. Tissue factor activity, tail bleeding time, and coagulation times remained unchanged under all conditions, indicating an unaltered state of vessel wall tissue factor, systemic coagulation and platelet function, respectively. Conclusions: Stress enhances arterial thrombosis via the sympathetic nervous system. The link between increased sympathetic activity and thrombus formation is still under investigation. These findings may open novel perspectives for the understanding of stress-induced cardiovascular events.

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