Tissue Factor and Cardiovascular Disease: Quo Vadis?

Abstract

The coagulation cascade represents a system of proteases responsible to maintain vascular integrity and to induce rapid clot formation after vessel injury. Tissue factor (TF), the key initiator of the coagulation cascade, binds to factor VIIa and thereby activates factor IX and factor X, resulting in thrombus formation. Different stimuli enhance TF gene expression in endothelial and vascular smooth muscle cells. In addition to these vascular cells, TF has recently been detected in the bloodstream in circulating cells such as leukocytes and platelets, as a component of microparticles, and as a soluble, alternatively spliced form of TF. Various cardiovascular risk factors like hypertension, diabetes, and dyslipidemia, increase levels of TF. In line with this observation, enhanced vascular TF expression occurs during atherogenesis, particularly in patients with acute coronary syndromes. (Circ J 2010; 74: 3 - 12)

Microvesicles and diabetic complications — novel mediators, potential biomarkers and therapeutic targets

“…The procoagulant effects of MVs are mainly due to the exposure of negatively charged PS [37] and tissue factor (TF) [2,6,7,37,38] , which are involved in the coagulation cascade. The negatively charged membrane lipid PS enhances clot propagation.…”

“…The negatively charged membrane lipid PS enhances clot propagation. TF is a transmembrane molecule, which has been identified on monocyte-derived MVs and endothelial-derived MVs [38] . TF-containing MVs in the blood stream may bind to activated platelets through interaction between P-selectin glycoprotein ligand-1 (PSGL-1, on the MVs) and P-selectin (on the platelet surface) [39] .…”

New perspectives and recommendations for anticoagulant therapy post orthopedic surgery

“…That cascade provides a sophisticated mechanism of signal amplification (Rang et al, 2003). However, under normal conditions, such amplification is carefully controlled by physiological inhibitors such as inhibitor of tissue factor pathway, antithrombin III (ATIII), an inhibitor of thrombin, and activated protein Can inhibitor of factors VIIIa and Va (Breitenstein, Tanner, Lüscher, 2010). There are two pathways which culminate in fibrin formation: 1) the intrinsic pathway -all its components are present in the blood; and 2) extrinsic pathway -some factors are external to the vasculature.…”

Blood-born tissue factor in cardiovascular disease: where are we now?

“…It is therefore conceivable that platelet associated, functionally active, TF might be delivered by these cells at the site of thrombus formation thus contributing to its growth. However, other potential sources of circulating TF have been reported and summarized in a recent review [13]. These are monocytes and macrophages, granulocytes and microparticles, mostly of platelet origin, but the TF is also released by red blood cells, granulocytes, monocytes, lymphocytes, endothelial cell and smooth muscle cells.…”

“…Pharmacological treatment of these conditions reduces TF over-expression [13]. Brambilla [15] recently report that platelet TF is higher in patients with ACS when compared with normal subjects and to patients with stable angina, and that TF over-expression in ACS patients is associated with an increase in platelet TF mRNA.…”