Lipid-bound factor Xa regulates tissue factor activity.

The activation of coagulation factor X by tissue factor (TF) and coagulation factor VIIa (VIIa) on a phospholipid surface is thought to be the key step in the initiation of blood coagulation. In this reaction, the product, fXa, is transiently and reversibly bound to the TF-VIIa enzyme complex. This in effect leads to a probabilistic inhibition of subsequent fX activations; a new fX substrate molecule cannot be activated until the old fXa molecule leaves.

Phospholipid surfaces regulate the delivery of substrate to tissue factor:VIIa and the removal of product.

For many years, the essential role of tissue factor (TF) in coagulation and thrombogenesis has been recognized. The catalytic complex of TF and VIIa (TF:VIIa) is membrane-bound whereas its substrate, factor X (FX), is distributed between a phospholipid-bound fraction and one that is in true solution in 3-dimensional space. This complicates analytical solutions for the kinetic mechanisms describing this reaction because dimensionality must be preserved.

Phospholipid regulates the activation of factor X by tissue factor/factor VIIa (TF/VIIa) via substrate and product interactions.

Although the phospholipid requirement for tissue factor (TF) activity has been well-established, the mechanism by which the surface regulates enzymatic activity remains unclear. We added phospholipid vesicles to already relipidated TF (30/70 PS/PC) and found that added lipid can both enhance and inhibit the rate of factor X (F.X) activation.

Alterations in myocardial tissue factor expression and cellular localization in dilated cardiomyopathy.

Objectives: We investigated the myocardial localization and expression of tissue factor (TF) and alternatively spliced human tissue factor (asHTF) in patients with dilated cardiomyopathy (DCM).

Background: Tissue factor is expressed in cardiac muscle and may play a role in maintaining myocardial structure.

Methods: Myocardial biopsies were obtained from patients with a normal or mildly impaired ejection fraction (EF) (> or =50%) and moderate to severely reduced EF (<50%).

Platelet deposition inhibits tissue factor activity: in vitro clots are impermeable to factor Xa.

Upon plaque rupture or vascular injury, tissue factor (TF) protein in the vessel wall becomes exposed to flowing blood, initiating a cascade of reactions resulting in the deposition of fibrin and platelets on the injured site. Paradoxically, the growing thrombus may act as a barrier, restricting the convective and diffusive exchange of substrates and coagulation products between the blood and reactive vessel wall, thus limiting the role TF plays in thrombus growth. In this study, various in vitro, platelet-fibrin clots were prepared on TF:VIIa-coated surfaces and the rate at which factor (F) X in the well-mixed clot supernatant permeates the clot and is converted to X(a) was monitored over several hours.

Alternatively spliced human tissue factor: a circulating, soluble, thrombogenic protein.

Tissue factor (TF) is an essential enzyme activator that forms a catalytic complex with FVII(a) and initiates coagulation by activating FIX and FX, ultimately resulting in thrombin formation. TF is found in adventitia of blood vessels and the lipid core of atherosclerotic plaques. In unstable coronary syndromes, plaque rupture initiates coagulation by exposing TF to blood.

Role of risk factors in the modulation of tissue factor activity and blood thrombogenicity.

Background: Several studies suggest a role for an increased circulating pool of tissue factor (TF) in atherothrombotic diseases. Furthermore, certain cardiovascular risk factors, such as diabetes, hyperlipemia, and smoking, are associated with a higher incidence of thrombotic complications. We hypothesized that the observed increased blood thrombogenicity (BT) observed in patients with type 2 diabetes mellitus may be mediated via an increased circulating tissue factor activity.

Local shear conditions and platelet aggregates regulate the incorporation and activity of circulating tissue factor in ex-vivo thrombi.

The presence of thrombogenic blood-borne or circulating tissue factor (cTF) has recently been demonstrated. These observations have implicated cTF to be a key determinant of thrombus propagation by depositing on platelets in nascent thrombi. Previously, we detected cTF by detergent solubilization and addition of phospholipids.

Platelets, circulating tissue factor, and fibrin colocalize in ex vivo thrombi: real-time fluorescence images of thrombus formation and propagation under defined flow conditions.

Although it is generally accepted that the initial event in coagulation and intravascular thrombus formation is the exposure of tissue factor (TF) to blood, there is still little agreement about the mechanisms of thrombus propagation and the identities of the molecular species participating in this process. In this study, we characterized the thrombotic process in real-time and under defined flow conditions to determine the relative contribution and spatial distribution of 3 components of the thrombi: circulating or blood-borne TF (cTF), fibrin, and platelets. For this purpose, we used high-sensitivity, multicolor immunofluorescence microscopy coupled with a laminar flow chamber.

Coronary no-reflow is caused by shedding of active tissue factor from dissected atherosclerotic plaque.

Defined angiographically, no-reflow (NR) manifests as an acute reduction in coronary flow in the absence of epicardial vessel obstruction. One candidate protein to cause coronary NR is tissue factor (TF), which is abundant in atherosclerotic plaque and a cofactor for activated plasma coagulation factor VII. Scrapings from atherosclerotic carotid arteries contained TF activity (corresponding to 33.