Fibrin clot structure and function are major determinants of Ball - Bat - Slo Pitch venous and arterial thromboembolic diseases, as well as the key determinants of the efficiency of clot lysis.Studies have revealed that fungi fibrinolytic compound 1 (FGFC1) is a novel marine pyranisoindolone natural product with fibrinolytic activity.Here, we explore the impacts of FGFC1 on clot structure, lysis, and plasminogen activation in vitro using turbidimetric, enzyme-linked immunosorbent assay, confocal and electron microscopy, urokinase, or plasmin chromogenic substrate.Clots formed in the presence of FGFC1 expressed reduced fibrin polymerization rate and maximum turbidity; however, they did not influence the lag phase of fibrin polymerization.
In the absence of scu-PA (single-chain urokinase plasminogen activator), microscopy revealed that FGFC1 increased the number of protofibrils within fibrin fiber and the pore diameter between protofibrils, inducing clots to form a region of thinner and looser networks separated by large pores.The effects of FGFC1 on Marble Run scu-PA-mediated plasma clot structure were similar to those in the absence of scu-PA.In addition, FGFC1 promoted the lysis of clots and increased the D-dimer concentration in lysate.FGFC1 increased the generation rate of p-nitroaniline in plasma.
These results show that FGFC1 has fibrinolytic activity in plasma, leading to interference with the release of fibrinopeptide B to affect lateral aggregation of protofibrils and increase clot susceptibility to fibrinolysis by altering its structure.