Role of tissue factor in thrombosis. Coagulation-inflammation-thrombosis circuit.
Tissue factor (TF) plays a role in thrombogenesis. TF initiates blood coagulation resulting in the generation of protease coagulant mediators (FVIIa, FXa, and FIIa) and fibrin production. TF hypercoagulablility directly contributes to thrombus formation resulting from the major events of fibrin deposition and FIIa-induced platelet activation/aggregation. In addition, blood coagulation indirectly promotes thrombogenicity via the coagulation-inflammation cycle in which TF plays a diverging and converging role. As the consequence of coagulation-dependent inflammation in which protease-activated receptor (PAR) mediates the coagulant signaling to elicit cytokines, selectins, and growth factors, such inflammation facilitates thrombosis by platelet aggregation and leukocyte recruitment. As TF hypercoagulability concerned, anti-thrombotic strategies involve the prevention by anticoagulation and PAR antagonism. Anticoagulants block the direct and indirect thrombotic contributions, while PAR antagonists arrest coagulation-dependent inflammation. With respect to both thrombosis and inflammation being cardiovascular risk factors, such strategies offer diverse benefits to cardioprotection.
Chu
Arthur J
AJ
MRC, Shantou University, Shantou, Guangdong, 515063, PR China. ajchu91@hotmail.com
D000818:Animals; D001777:Blood Coagulation; D001808:Blood Vessels / Q000473:pathology; D002318:Cardiovascular Diseases / Q000473:pathology; D015942:Factor VIIa / Q000737:chemistry; D015951:Factor Xa / Q000737:chemistry; D005337:Fibrin / Q000737:chemistry; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D008954:Models, Biological; D009206:Myocardium / Q000473:pathology; D010455:Peptides / Q000737:chemistry; D010974:Platelet Aggregation; D011516:Prothrombin / Q000737:chemistry; D044462:Receptors, Proteinase-Activated / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism / Q000502:physiology*; D013927:Thrombosis / Q000473:pathology*
D010455:Peptides; D044462:Receptors, Proteinase-Activated; D011516:Prothrombin; D005337:Fibrin; C025337:Factor IIa; D013925:Thromboplastin; D015942:Factor VIIa; D015951:Factor Xa