Heterogeneity of plasma tissue factor pathway inhibitor.
Much of tissue factor pathway inhibitor (TFPI) in plasma is bound to lipoproteins. The major form of TFPI associated with low density lipoproteins (LDL) is 34 kDa, whereas that associated with high density lipoproteins (HDL) is 41 kDa and appears in part to represent a mixed disulphide complex between TFPI and apolipoprotein AII. The native and recombinant TFPI produced by mammalian cells in tissue culture and the TFPI released by heparin in vivo, however, are 34 kDa. Western blotting with antibodies raised against specific TFPI peptides and cation exchange chromatography under denaturing conditions of partially purified plasma TFPI suggest that only a fraction of TFPI circulating in plasma is in the form of the full length molecule, the remainder consisting of variably carboxyl-terminal truncated forms. Electrospray mass spectrometry of the isolated 34 kDa form of plasma TFPI, which predominantly circulates bound to LDL, confirms that it lacks a substantial portion of the carboxyl-terminus including at least a portion of the third Kunitz-type domain.
Division of Hematology, Jewish Hospital, Washington University Medical Center, St Louis, MO 63110.
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Broze
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Lange
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Duffin
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MacPhail
D000595:Amino Acid Sequence; D015153:Blotting, Western; D002846:Chromatography, Affinity; D002852:Chromatography, Ion Exchange; D006801:Humans; D008074:Lipoproteins / Q000737:chemistry* / Q000302:isolation & purification; D008077:Lipoproteins, LDL / Q000378:metabolism; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D010949:Plasma; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000378:metabolism
D008074:Lipoproteins; D008077:Lipoproteins, LDL; D011993:Recombinant Fusion Proteins; C051928:lipoprotein-associated coagulation inhibitor