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Tissue Factor Mediated Activation of Proteases in Purified Prothrombin Complex Concentrates is Inhibited by Mucosopolysaccharide Polysulfate. Results from the Studies on Proteinchip Array using SELDI
Author(s) -
Raake Wolfram,
FlorianKujawski M,
Hoppensteadt D,
Maddineni J,
Chyna B,
Fareed J
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a656-c
Subject(s) - proteases , chemistry , tissue factor pathway inhibitor , tissue factor , thrombin , protease , heparin , recombinant dna , prothrombinase , biochemistry , microbiology and biotechnology , enzyme , coagulation , immunology , biology , medicine , platelet , gene
Topical ointments containing sulfated mucopolysaccharide polysulfate (MPS) of mammalian origin are widely used in the management of thrombophlebitis and trauma associated inflammatory states. The molecular distribution profile of MPS is comparable to the low molecular heparin (LMWH) but the relative anticoagulant and antiprotease activity are lesser than LMWHs. Since tissue factor plays an important role in the mediation of trauma and inflammatory processes it was hypothesized that MPS may modulate its activity. To test this hypothesis, a protein chip array technique utilizing the surface enhanced laser desorption ionization (SELDI) was investigated to obtain the activation profile of prothrombin complex (PCC). PCC was activated using recombinant tissue factor to obtain a specific biomarker profile representing activated proteases and cleavage products. MPS produced direct inhibition of this process. When MPS was mixed with antithrombin (AT), heparin cofactor II (HC II) and tissue factor pathway inhibitor (TFPI) stronger inhibitory effects were noted. TFPI, AT and HC II also produced inhibition of the generation of such proteases as factor Xa, and MPS amplified these effects. These results suggest that the therapeutic effects of MPS may be related to its modulation of the protease generation. It is proposed that MPS produces multiple actions including the inhibition of TF mediated protease generation.