Relevance of tissue factor in cardiovascular disease.
Overexpression and exposition of tissue factor (TF) in atherosclerotic plaques and/or arterial thrombi are critical events in atherothrombosis. TF, the receptor for factor VII (FVII) and activated factor VII (FVIIa), is the principal initiator of blood coagulation and induces thrombin generation leading to fibrin formation and platelet activation. TF also plays a major role in cell migration and angiogenesis. TF activity is downregulated by Tissue Factor Pathway Inhibitor (TFPI), a Kunitz-type inhibitor, which forms a neutralizing complex with TF, FVIIa and activated factor X. In physiological conditions, TF is absent from vascular cells which come into contact with flowing blood and is present as an inactive pool in fibroblasts and smooth muscle cells (SMC). In contrast, TF is widely expressed in atherosclerotic plaques and is found in macrophages, SMCs, and foam-cells and also in extracellular matrix and acellular lipid-rich core. TF expression is up-regulated by inflammatory cytokines and oxidized lipids. Plaque thrombogenicity is directly correlated to their TF content. After fibrous cap disruption, TF is exposed on plaque surface and triggers thrombus formation leading to arterial lumen occlusion and/or downstream embolization. In coronary and carotid plaques, TF content was found to be higher in plaques from symptomatic than asymptomatic patients. Soluble forms of TF and microparticles of monocyte and platelet origin, and bearing TF, constitute "blood-born TF". The contribution of this TF pool to arterial thrombosis is still under discussion. TF pathway is a target for new therapeutic agents that can decrease TF activity, such as active site-inactivated factor VIIa, recombinant TFPI and antibodies against TF or peptides interfering with TF-FVIIa complex activity.
Jude
B
B
INSERM-ERI-9, université de Lille 2, EA 2693, centre hospitalier régional universitaire, Institut d'hématologie, Lille. b-jude@chru-lille.fr
Zawadzki
C
C
Susen
S
S
Corseaux
D
D
D001161:Arteriosclerosis / Q000503:physiopathology*; D002318:Cardiovascular Diseases / Q000503:physiopathology*; D002465:Cell Movement; D005347:Fibroblasts / Q000502:physiology; D006490:Hemostatics / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation; D009130:Muscle, Smooth / Q000502:physiology; D009389:Neovascularization, Pathologic; D013925:Thromboplastin / Q000096:biosynthesis / Q000502:physiology*
D006490:Hemostatics; D013925:Thromboplastin