کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2552320 | 1560721 | 2009 | 6 صفحه PDF | دانلود رایگان |

AimsSeveral activated coagulation factors have been reported to enhance fibrinolysis by inactivating plasminogen activator inhibitor type 1 (PAI-1), a serine protease inhibitor. We analyzed the interaction between PAI-1 and the three serine proteases generated during contact activation of plasma, activated factor XII (FXIIa), FXIa, and kallikrein, and evaluated their effects on fibrinolysis in-vitro.Main methodsEffects of kaolin on euglobulin clot lysis time (ECLT) and behavior of PAI-1 in factor-depleted plasma were analyzed.Key findingsThe ECLT of pooled plasma obtained from normal volunteers (designated as 100%) was shortened to 62.1 ± 3.1% by Ca2+ (5 mM) and 29.9 ± 3.1% by kaolin. Activated protein C reversed the ECLT shortened by Ca2+-supplementation (86.3 ± 17.4%), but did not affect the ECLT shortened by kaolin (31.4 ± 2.1%). Thus, in contrary to Ca2+-supplementation, kaolin appeared to shorten the ECLT by a mechanism independent of thrombin generation. In three kinds of contact factor-depleted plasma, kaolin did not shorten ECLT only in FXII-depleted plasma. PAI-1 was cleaved to its inactive form in the Ca2+ as well as the kaolin-supplemented euglobulin fraction in normal plasma, the latter of which, however, was not observed in FXII-depleted plasma. Similarly, a high molecular weight complex between FXIIa and PAI-1, as well as a cleaved form of PAI-1, was observed in kaolin-supplemented normal plasma, but neither was found in kaolin-supplemented FXII-depleted plasma.SignificancePAI-1 inactivation by FXIIa appears to be a mechanism by which contact phase coagulation factors enhance fibrinolysis independently of thrombin generation.
Journal: Life Sciences - Volume 85, Issues 5–6, 29 July 2009, Pages 220–225