In Vivo Degradation of Human Fibrinogen Aα: Detection of Cleavage Sites and Release of Antithrombotic Peptides

Abstract

Several degradation products of fibrinogen have been shown to possess regulatory functions. Using peptide exacts from human blood filtrate, a large number of fibrinogen Aα fragments was identified. These fragments are generated at known plasmin attack sites and at several novel cleavage sites especially at hydrophobic and basic amino acid residues. One fragment containing the cell attachment site (RGD sequence) of fibrinogen Aα efficiently inhibits fibrinogen binding and platelet aggregation (IC 50: 20-50 μM) in vitro. We conclude that in vivo degradation of fibrinogen Aα results in generation of endogenous antithrombotic peptides with local importance in fibrinolysis and platelet aggregation.