Tissue factor and coronary artery disease.
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.
Moons
Arno H M
AH
Department of Cardiology, Academic Medical Center, Room F3-236, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Levi
Marcel
M
Peters
Ron J G
RJ
D000208:Acute Disease; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects; D000804:Angiotensin II; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000925:Anticoagulants / Q000627:therapeutic use; D001120:Arginine / Q000627:therapeutic use; D001241:Aspirin / Q000627:therapeutic use; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000378:metabolism*; D003328:Coronary Thrombosis / Q000188:drug therapy / Q000378:metabolism*; D016572:Cyclosporine / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000378:metabolism; D015942:Factor VIIa / Q000627:therapeutic use; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use; D024764:Hirudin Therapy; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D011994:Recombinant Proteins / Q000627:therapeutic use; D013917:Thrombin / Q000037:antagonists & inhibitors; D013925:Thromboplastin / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D000960:Hypolipidemic Agents; D011994:Recombinant Proteins; D000804:Angiotensin II; D016572:Cyclosporine; D013925:Thromboplastin; D001120:Arginine; D015942:Factor VIIa; D013917:Thrombin; D001241:Aspirin