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Inactivation of plasminogen activator inhibitor type 1 by activated factor XII plays a role in the enhancement of fibrinolysis by contact factors in-vitro.
Life Sci. 2009 Jul 31; 85(5-6):220-5.LS

Abstract

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 Ca(2+) (5 mM) and 29.9+/-3.1% by kaolin. Activated protein C reversed the ECLT shortened by Ca(2+)-supplementation (86.3+/-17.4%), but did not affect the ECLT shortened by kaolin (31.4+/-2.1%). Thus, in contrary to Ca(2+)-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 Ca(2+) 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.

Authors+Show Affiliations

Department of Physiology, Hamamatsu University School of Medicine, Hamamatsu, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19500599

Citation

Tanaka, Aki, et al. "Inactivation of Plasminogen Activator Inhibitor Type 1 By Activated Factor XII Plays a Role in the Enhancement of Fibrinolysis By Contact Factors In-vitro." Life Sciences, vol. 85, no. 5-6, 2009, pp. 220-5.
Tanaka A, Suzuki Y, Sugihara K, et al. Inactivation of plasminogen activator inhibitor type 1 by activated factor XII plays a role in the enhancement of fibrinolysis by contact factors in-vitro. Life Sci. 2009;85(5-6):220-5.
Tanaka, A., Suzuki, Y., Sugihara, K., Kanayama, N., & Urano, T. (2009). Inactivation of plasminogen activator inhibitor type 1 by activated factor XII plays a role in the enhancement of fibrinolysis by contact factors in-vitro. Life Sciences, 85(5-6), 220-5. https://doi.org/10.1016/j.lfs.2009.05.014
Tanaka A, et al. Inactivation of Plasminogen Activator Inhibitor Type 1 By Activated Factor XII Plays a Role in the Enhancement of Fibrinolysis By Contact Factors In-vitro. Life Sci. 2009 Jul 31;85(5-6):220-5. PubMed PMID: 19500599.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inactivation of plasminogen activator inhibitor type 1 by activated factor XII plays a role in the enhancement of fibrinolysis by contact factors in-vitro. AU - Tanaka,Aki, AU - Suzuki,Yuko, AU - Sugihara,Kazuhiro, AU - Kanayama,Naohiro, AU - Urano,Tetsumei, Y1 - 2009/06/03/ PY - 2009/02/18/received PY - 2009/05/07/revised PY - 2009/05/23/accepted PY - 2009/6/9/entrez PY - 2009/6/9/pubmed PY - 2009/7/31/medline SP - 220 EP - 5 JF - Life sciences JO - Life Sci VL - 85 IS - 5-6 N2 - 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 Ca(2+) (5 mM) and 29.9+/-3.1% by kaolin. Activated protein C reversed the ECLT shortened by Ca(2+)-supplementation (86.3+/-17.4%), but did not affect the ECLT shortened by kaolin (31.4+/-2.1%). Thus, in contrary to Ca(2+)-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 Ca(2+) 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. SN - 1879-0631 UR - https://www.unboundmedicine.com/medline/citation/19500599/Inactivation_of_plasminogen_activator_inhibitor_type_1_by_activated_factor_XII_plays_a_role_in_the_enhancement_of_fibrinolysis_by_contact_factors_in_vitro_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024-3205(09)00242-2 DB - PRIME DP - Unbound Medicine ER -