Clearance of Tissue Plasminogen Activator (TPA) and TPA/Plasminogen Activator Inhibitor Type 1 (PAI-1) Complex

Abstract

Plasma clearance of active TPA was faster than clearance of TPA/PAI-1 complex. High levels of active PAI-1 converted more TPA into TPA/PAI-1 complex, effectively slowing the clearance of total TPA antigen and explaining in part why high levels of PAI-1 activity are associated with increases in total TPA antigen.

The effects of whole body vibration and exercise on fibrinolysis in men

“…It is unclear why the PAI-1 change in the VX trial was not different than the X trial, similar to the change in tPA activity. During exercise plasma concentration of active PAI-1 decreases primarily by PAI-1 binding to tPA, forming a tPA/PAI-1 complex (12). Since tPA activity increased more during the VX trial than the X condition, it would be expected that increasing platelet aggregation will also increase the release of PAI-1.…”

“…tPA is the primary stimulator of fibrinolysis, while PAI-1 is the primary inhibitor. Fibrinolytic activity is stimulated by a number of factors including epinephrine, low blood glucose, shear stress placed on endothelial cells of blood vessels (15) and exercise (8,12,26). Low fibrinolytic potential is associated with an increased risk for an ischemic event (18, 26).…”

Angiotensin-Converting Enzyme Inhibition Increases Human Vascular Tissue-Type Plasminogen Activator Release Through Endogenous Bradykinin

“…4 In addition, ACE inhibitors have been shown to improve fibrinolytic balance by decreasing circulating concentrations of plasminogen activator inhibitor-1 (PAI-1), the major physiological inhibitor of tissue type plasminogen activator (t-PA). [5][6][7] The findings in several studies that ACE inhibitors decrease PAI-1 without decreasing t-PA antigen 6,8,9 (which reflects both free active t-PA and t-PA bound to PAI-1 and other inhibitors 10 ) suggested that ACE inhibitors may increase t-PA release through effects on endogenous bradykinin (BK). Indeed, there is substantial evidence that exogenous BK stimulates t-PA release from the human forearm vasculature 11 and that ACE inhibition potentiates this effect in the peripheral 12 and coronary vasculature.…”

The impact of angiotensin II receptor blockade and the DASH diet on markers of endogenous fibrinolysis

“…However, we saw no significant effect of losartan on t-PA activity. Since active t-PA and PAI-1 enzymes are cleared more rapidly than the t-PA/PAI-1 complex, 34 it is possible that changes in t-PA antigen could occur independent of changes in enzyme activities. Finally, the lack of effect of losartan on PAI-1 enzyme activity in the current study is consistent with the hypothesis that effects of AII on PAI-1 are mediated by a non-AT1 receptor.…”

“…19,40,41 The paradoxical association of increased risk of CVD events and increased t-PA antigen is likely due to the fact that t-PA clearance is largely dependent on PAI-1. 34 Because most circulating t-PA antigen is bound to PAI-1, elevated levels of t-PA antigen likely reflect resistance to fibrinolysis. The results of this study suggest that favourable effects on fibrinolytic factors may mediate some of the reduction in cardiovascular disease risk obtained from pharmacologic inhibition of AII.…”