The role of fibrinogen variants in cardiovascular diseases and wound healing

Maintaining the integrity and patency of the vascular system is essential for the viability of humans. When vascular injury has occurred, fast formation of a thrombus at the site of injury is essential to seal the wound, resulting in haemostasis. Haemostasis is a tightly regulated process, which involves the activation of endothelial cells, platelets, procoagulants and the inhibition of fibrinolytic factors. Haemostasis can be separated in two phases called primary and secondary haemostasis, which occur simultaneously.1 In primary haemostasis, a platelets plug is rapidly formed at the site of injury, whereas in secondary haemostasis, blood coagulation is initiated, either with negatively charged surfaces (intrinsic pathway) or with tissue factor (extrinsic pathway). The cascade leads to the generation of thrombin and the formation of a fibrin network.2 The thrombus provides an effective restriction for bleeding. Hence, an imbalance of normal haemostasis caused by pathologic disorders may lead to thrombosis or hemorrhage, which may account for morbidity and mortality. Fibrinogen is a central protein in the hemostatic system. At the final stage of the blood coagulation system, thrombin converts the soluble fibrinogen into fibrin monomers, which then polymerize to an insoluble fibrin clot. Furthermore, fibrinogen induces platelet adhesion and aggregation via the αIIbβ3 integrin, thus promoting blood coagulation. In addition to their primary function in blood clotting, fibrinogen and fibrin also play a role in various physiological reactions including fibrinolysis, cellular and matrix interactions, wound healing and neoplasia.

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