Tissue factor and coronary artery disease

Abstract

Plaque disruption with superimposed thrombosis is the main cause of acute coronary events such as acute myocardial infarction and unstable angina. Among other factors, tissue factor seems to play an important role determining plaque thrombogenicity. Tissue factor is a potent initiator of the coagulation cascade situated within the vessel wall and is highly exposed to the blood after plaque rupture. Several mediators involved in the process of atherosclerotic plaque formation are capable of inducing tissue factor expression in cells such as monocytes, macrophages and endothelial cells, which under normal conditions do not express tissue factor or to a limited extent only. The increased expression of tissue factor is not limited to the plaque but is also found in circulating monocytes in patients with acute coronary syndromes. In addition, studies have shown an important contribution of tissue factor in the pathogenesis of thrombosis and restenosis after balloon angioplasty. Recent basic studies focus on the therapeutic inhibition of tissue factor. Specific and non-specific inhibitors of tissue factor or the tissue factor/factor VIIa complex have been developed or identified, and have been tested in experimental studies. Clinical studies are currently being initiated. In this review, we present the current knowledge on the role of tissue factor in atherosclerosis, arterial intervention and potential pharmacological approaches, with focus on acute coronary syndromes.

Prominent Lectin-Like Oxidized Low Density Lipoprotein (LDL) Receptor-1 (LOX-1) Expression in Atherosclerotic Lesions Is Associated with Tissue Factor Expression and Apoptosis in Hypercholesterolemic Rabbits

“…5) Tissue factor (TF), a cofactor for plasma coagulation factor VIIa, which is localized in vascular cells and the lipid core within the atherosclerotic lesions, is an initiator of the coagulation cascade leading to thrombus formation after the plaque rupture in vivo. 3) Lectin-like oxidized low density lipoprotein (LDL) receptor-1 (LOX-1), a type II membrane glycoprotein belonging to the C-type lectin family, acts as a cell-surface receptor for oxidized LDL (Ox-LDL) and mediates several biological effects of Ox-LDL. 6) Recent studies with cultured cells suggest that LOX-1 may play several important roles in destabilization of atherosclerotic plaques, inducing expression of adhesion molecules and chemokines for monocytes, 7) transformation of macrophages into foam cells, 8,9) apoptosis of smooth muscle cells 10,11) and the degradation of extracellular matrix proteins by induction of matrix metalloproteinases.…”

Plaque, Platelets, and Plug – The Pathogenesis of Acute Coronary Syndrome

“…Two important direct platelet agonists dwell in the lipid-rich core, i.e lysophosphatidic acid which mediates platelet shape change during thrombus formation and collagen which induces platelet adhesion and aggregation (Lusis, 2000). Tissue factor, another major thrombogenic subtrate in the lipid-rich core, is released by endothelial cells, smooth muscle cells, monocytes and macrophages or foam cells (Moons et al, 2002). The most abundant tissue factor site is in the necrotic core (Moons et al, 2002).…”

“…Tissue factor, another major thrombogenic subtrate in the lipid-rich core, is released by endothelial cells, smooth muscle cells, monocytes and macrophages or foam cells (Moons et al, 2002). The most abundant tissue factor site is in the necrotic core (Moons et al, 2002). Tissue factor activates coagulation cascade and promotes thrombus stabiliy through fibrin network formation.…”

DMSO inhibits human platelet activation through cyclooxygenase-1 inhibition. A novel agent for drug eluting stents?

“…Initiation of a luminal thrombosis involves both activation of the coagulation cascade by TF and factor VII [18,22,23,33], and platelet activation [13,26].…”