Pathophysiologic roles of the fibrinogen gamma chain

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Purpose of review: Fibrinogen binds through its γ 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 γ chain in these processes, and illustrates the potential for therapeutic intervention. Recent findings: Novel γ chain epitopes that bind platelet integrin α, IIbβ3 and leukocyte integrin α Mβ2 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 γ 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 γ 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 γ′ chain has also become clearer. Studies have shown that γ′ chain binding to thrombin and factor XIII results in clots that are mechanically stiffer and resistant to fibrinolysis, which may explain the association between γA/γ′ fibrinogen levels and cardiovascular disease. Summary: The identification of new interactions with γ chains has revealed novel targets for the treatment of inflammation and thrombosis. In addition, several exciting studies have shown new functions for the variant γ′ chain that may contribute to cardiovascular disease.

Original languageEnglish (US)
Pages (from-to)151-155
Number of pages5
JournalCurrent Opinion in Hematology
Volume11
Issue number3
DOIs
StatePublished - May 2004

Fingerprint

Fibrinogen
Clot Retraction
Thrombosis
Blood Platelets
Inflammation
Platelet Aggregation
Integrins
Wound Healing
Cardiovascular Diseases
Factor XIIIa
Factor XIII
Blood Coagulation Factors
Cell Surface Receptors
Fibrinolysis
Fibroblast Growth Factor 2
Fibrin
Thrombin
Epitopes
Intercellular Signaling Peptides and Proteins
Leukocytes

Keywords

  • Coagulation
  • Hemostasis
  • Inflammation
  • Platelets
  • Thrombosis

ASJC Scopus subject areas

  • Hematology

Cite this

Pathophysiologic roles of the fibrinogen gamma chain. / Farrell, David.

In: Current Opinion in Hematology, Vol. 11, No. 3, 05.2004, p. 151-155.

Research output: Contribution to journalArticle

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