Determinants of fibrin formation, structure, and function

Abstract

Fibrinogen is the protein substrate of the multifaceted procoagulant and proinflammatory enzyme, thrombin. Fibrin, the product of thrombin's proteolytic cleavage of fibrinogen, provides biophysical and biochemical support to blood clots, and subsequent degradation of fibrin by plasmin is a critical inflammatory mediator and essential step in wound healing. As such, fibrin(ogen) lies at the nexus of vascular injury and repair. Herein, we review aspects of fibrin(ogen) formation, structure, stability, and function, focusing on novel findings within the past 2 years. Early research into specific properties of fibrinogen and fibrin revealed complex kinetics by which fibrinogen is converted to a fibrin network in vitro. These findings laid important groundwork for current in-vivo studies on the role of fibrin(ogen) in hemostasis and thrombosis. Recent studies show novel mechanisms regulating fibrinogen expression, as well as novel roles of fibrinogen in infection, inflammation, and cognitive disorders. Expression of fibrinogen and interactions between fibrinogen and other proteins are essential for homeostasis. However, recent findings show abnormal fibrinogen modifications and/or increased fibrin formation and network stability promote thrombosis, as well as disorders not previously associated with coagulation. These findings highlight the increasingly important role of fibrin(ogen) in health and disease.