Journal
CURRENT OPINION IN HEMATOLOGY
Volume 11, Issue 3, Pages 151-155Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/01.moh.0000131440.02397.a4
Keywords
coagulation; hemostasis; inflammation; platelets; thrombosis
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Purpose of review Fibrinogen binds through its gamma chains to cell surface receptors, growth factors, and coagulation factors to perform its key roles in fibrin clot formation, platelet aggregation, and wound healing. However, these binding interactions can also contribute to pathophysiologic processes, including inflammation and thrombosis. This review summarizes the latest findings on the role of the fibrinogen gamma chain in these processes, and illustrates the potential for therapeutic intervention. Recent findings Novel gamma chain epitopes that bind platelet integrin alpha(IIb)beta(3), and leukocyte integrin alpha(M)beta(2) have been characterized, leading to the revision of former dogma regarding the processes of platelet aggregation, clot retraction, inflammation, and thrombosis. A series of studies has shown that the gamma chain serves as a depot for fibroblast growth factor-2 (FGF-2), which is likely to play an important role in wound healing. Inhibition of gamma chain function with the monoclonal antibody 7E9 has been shown to interfere with multiple fibrinogen activities, including factor XIIIa crosslinking, platelet adhesion, and platelet-mediated clot retraction. The role of the enigmatic variant fibrinogen gamma' chain has also become clearer. Studies have shown that gamma' chain binding to thrombin and factor XIII results in clots that are mechanically stiffer and resistant to fibrinolysis, which may explain the association between gammaA/gamma', fibrinogen levels and cardiovascular disease. Summary The identification of new interactions with gamma chains has revealed novel targets for the treatment of inflammation and thrombosis. In addition, several exciting studies have shown new functions for the variant gamma' chain that may contribute to cardiovascular disease.
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