Tissue factor in the myocardium: evidence of roles in haemostasis and inflammation.
The interaction between cell-surface tissue factor (TF) and the plasma coagulation factor VII (FVII) initiates the coagulation network that leads to the generation of thrombin and the formation of a fibrin clot. Thrombin also activates cellular protease activated receptors (PARs) through which it activates components of the inflammatory pathway. TF is expressed constitutively by cardiomyocytes and evidence from mice transgenic for a human TF mini-gene that express very low levels of human TF suggests that the TF-FVII interaction is critical for haemostasis within the heart. Pathological contact between TF and FVII may occur in the heart during ischaemia-reperfusion (I-R) injury and this may lead to activation of coagulation and thrombin generation. Evidence from animal models now suggests that thrombin is an important mediator of inflammation in I-R injury. The coagulation pathway therefore represents a novel therapeutic target for intervention in the prevention of I-R injury.
Mumford
Andrew D
AD
Department of Haematology, Bristol Royal infirmary, Bristol, BS2 8HW, UK. a.mumford@bristol.ac.uk
McVey
John H
JH
D000818:Animals; D005167:Factor VII / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D051379:Mice; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D015427:Reperfusion Injury; D013917:Thrombin / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism*; D019076:Transgenes
D005167:Factor VII; D013925:Thromboplastin; D013917:Thrombin