[From fibrinogen to fibrin and its dissolution].
Fibrinogen is a protein synthesised by the liver. It is converted by thrombin to an insoluble fibrin network to induce, together with platelet aggregates, haemostasis in response to rupture of endothelium. This change includes several steps and implied factor XIII. Molecular properties of fibrin are responsible for its important role in hemostasis which goes beyond the one of a simple final inert product of coagulation. In fact, fibrin regulates thrombin and factor XIII activities and its own destruction also called fibrinolysis. The multiple domains of fibrinogen and fibrin confer a role not only in haemostasis but also in wound healing, cellular migration and proliferation, due to interactions with endothelial cells, leukocytes and components of the extracellular matrix. Fibrin must be removed once its haemostatic role has been reached. The fibrinolytic process takes place in the vessel lumen. It is strongly regulated by the plasma concentration of an inhibitor called plasminogen activator inhibitor-1 (PAI-1) which synthesis strongly increases in obese insulin resistant and diabetic patients. Data from animal models show that increased PAI-1 production represents a prothrombotic state. Fibrinolysis plays also a role in tissue remodeling (vascular wall, placenta, adipose tissue....) by degrading the extracellular matrix, by activating growth factors or modifying cellular adhesion and migration properties. It has been proposed that PAI-1 in excess could be directly responsible for the development of atherothrombosis in insulin resistant subjects. Moreover recent results from transgenic mice indicate that PAI-1 in excess interferes also with weight gain. These data point out the importance of the haemostatic system in the extra vascular phenomenon of tissue remodeling.
Juhan-Vague
Irène
I
Laboratoire d'Hématologie, CHU Timone, INSERM EPI 9936-13385 Marseille.
Hans
Michel
M
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology*; D025901:Carboxypeptidase B2 / Q000502:physiology; D002465:Cell Movement; D003920:Diabetes Mellitus / Q000209:etiology / Q000503:physiopathology; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000502:physiology; D005176:Factor XIII / Q000502:physiology; D005337:Fibrin / Q000502:physiology*; D005340:Fibrinogen / Q000502:physiology*; D005342:Fibrinolysis; D006487:Hemostasis; D006801:Humans; D007333:Insulin Resistance; D045726:Metalloproteases / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000502:physiology; D012307:Risk Factors; D013917:Thrombin / Q000502:physiology; D013927:Thrombosis / Q000209:etiology*; D014945:Wound Healing / Q000502:physiology
D017395:Plasminogen Activator Inhibitor 1; D005337:Fibrin; D005340:Fibrinogen; D005176:Factor XIII; D045726:Metalloproteases; D025901:Carboxypeptidase B2; D013917:Thrombin