Comparison between the clot-protecting activity of a mutant plasminogen activator inhibitor-1 with a very long half-life and 6-aminocaproic acid

Abstract

Abstract. Plasminogen activator inhibitor (PAI)-1 is a serpin glycoprotein that can stabilize blood clots by inhibiting fibrinolysis. However, wild-type PAI-1 has the disadvantage of a short half-life of ~2 h. A very long half-life

RUNX1 and TGF‐β signaling cross talk regulates Ca2+ ion channels expression and activity during megakaryocyte development

“…5B), was about 10-fold up-regulated (Table 1). PAI-1 is involved in normal blood clotting by inhibiting the action of other proteins called plasminogen activators, which are involved in the activation of matrix metalloproteinases, cleavage of fibrin, and degradation of ECM components by activating plasminogen [44,45]. The THBS1 (thrombospondin-1) was observed with a 12.67-fold increase (Table 1) and is an adhesive glycoprotein, which associates with the ECM (Fig.…”

Temporary inhibition of the plasminogen activator inhibits periosteal chondrogenesis and promotes periosteal osteogenesis during appendicular bone fracture healing

“…Due to the short half-life and the short treatment interval (30 minutes prior to and 30 minutes post-fracture) we hypothesize that the treatment resulted in a biologically relevant change in the microenvironment of the early hematoma, that would then later trigger the observed cell fate shift (Fig. 1&2) [21]. To test this hypothesis, we employed two experimental strategies.…”

Characterization of the Annonaceous acetogenin, annonacinone, a natural product inhibitor of plasminogen activator inhibitor-1

“…TEG was chosen as it yields data on the whole coagulation profile (clot lysis, kinetics and dynamics)34. The Influence of tPA and PAI-1 addition on healthy human plasma was already measured by TEG35 and TEG was also already used to investigate the effect of small molecule PAI-1 inhibitor on human plasma36. As previously observed in TEG35, tPA-treated plasma had short lysis time and further addition of PAI-1 increased lysis time to a normal healthy plasma level.…”

“…The Influence of tPA and PAI-1 addition on healthy human plasma was already measured by TEG35 and TEG was also already used to investigate the effect of small molecule PAI-1 inhibitor on human plasma36. As previously observed in TEG35, tPA-treated plasma had short lysis time and further addition of PAI-1 increased lysis time to a normal healthy plasma level. Pre-incubation of PAI-1 with annonacinone completely inhibits PAI-1 anti-fibrinolytic activity of tPA-treated plasma in TEG and reduced clot lysis time more efficiently than tiplaxtinin.…”