[Role of tissue factor in atherothrombosis]

Tissue factor is a key enzyme in coagulation process. It is primary known as a cofactor for factor VIIa-mediated triggering of blood coagulation, which proceeds in a cascade of extracellular reactions. Tissue factor forms a catalytic complex with VIIa and intitiates coagulation by activating factor IX and X, ultimately resulting in thrombin formation. Being a transmembranic glycoprotein it takes a signalling information to another cell activity after endothelium or other tissue damage. Tissue factor plays a pivotal role in blood clotting physiology and pathology especialy in atherothrombosis. Thrombogenic tissue factor on cell-derived microparticles is present in the circulating blood of patients with acute coronary syndromes. Tissue factor is found in adventitia of blood vessels and the lipid core of atherosclerotic plaques (but not in vascular cells contacting directly with blood). Although the molecular mechanisms responsible for these phenomena remain unclear, it is thought that they are brought about by the action of intracellular signaling, resulting in gene transcription and subsequent protein synthesis. By expressing on monocyte or macrofage cell membrane surface it is involved in proinflammatory action and plaque destabilisation. This shifted the emphasis to investigations of what happened on the cell surface, and later to the cell biology of tissue factor and its inducibility in monocytes/macrophages and endothelial cells. Recent studies have suggested that tissue factor also plays non-hemostatic roles in blood vessel development, tumor angiogenesis and metastasis, inflamation. Tissue factor upregulates a number of genes involved in regulation of growth, transcription, and cellular motility, as well as cytokines, makes it possible to suggest a link between the formation of the tissue factor / VIIa complex and the cellular processes. Regulation of tissue factor activity by natural tissue factor pathway inhibitor (synthesized by vascular endothelial cells) or by special drugs is a new insight in thrombosis and vessel reocclusion preventive therapy. Tissue factor concentration in circulating blood has a higher informativity comparing to troponine and CRB values.