Inactivation of plasminogen activator inhibitor type 1 by activated factor XII plays a role in the enhancement of fibrinolysis by contact factors in-vitro

Aki Tanaka, Yuko Suzuki, Kazuhiro Sugihara, Naohiro Kanayama, Tetsumei Urano

研究成果: Article査読

14 被引用数 (Scopus)

抄録

Aims: Several 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 methods: Effects of kaolin on euglobulin clot lysis time (ECLT) and behavior of PAI-1 in factor-depleted plasma were analyzed. Key findings: The 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. Significance: PAI-1 inactivation by FXIIa appears to be a mechanism by which contact phase coagulation factors enhance fibrinolysis independently of thrombin generation.

本文言語English
ページ(範囲)220-225
ページ数6
ジャーナルLife Sciences
85
5-6
DOI
出版ステータスPublished - 29-07-2009
外部発表はい

All Science Journal Classification (ASJC) codes

  • 生化学、遺伝学、分子生物学(全般)
  • 薬理学、毒性学および薬学(全般)

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