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- W2750934433 abstract "Mouse models can provide insight into the pathophysiology of human thrombosis and hemostasis. Tissue factor pathway inhibitor (TFPI) regulates coagulation through protein S (PS)‐enhanced factor (F) Xa inhibition and FXa‐dependent inhibition of FVIIa/tissue factor (TF) activity. TFPI is expressed as isoforms α and β in man, and α, β and γ in the mouse.Assess the reliability of extending TFPI‐related studies in mice to humans.Compare mouse and human TFPI physiology using a variety of methods.Mouse TFPI and human TFPI are similar in regard to: (i) the mechanisms for FVIIa/TF and FXa inhibition; (ii) TFPIα is a soluble form and TFPIβ is glycosyl phosphatidyl inositol (GPI) membrane anchored; (iii) the predominant circulating form of TFPI in plasma is lipoprotein‐associated; (iv) low levels of TFPIα circulate in plasma and increase following heparin treatment; and (v) TFPIα is the isoform in platelets. They differ in that: (i) mouse TFPI circulates at a ~20‐fold higher concentration; (ii) mouse lines with isolated isoform deletions show this circulating mouse TFPI is derived from TFPIγ; (iii) sequences homologous to the mouse TFPIγ exon are present in many species, including man, but in primates are unfavorable for splicing; and (iv) tandem mass spectrometry (MS/MS) detects sequences for TFPI isoforms α and β in human plasma and α and γ in mouse plasma.To dissect the pathophysiological roles of human TFPIα and TFPIβ, studies in TFPIγ null mice, expressing only α and β, only α or only β should better reflect the human situation." @default.
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- W2750934433 date "2017-09-01" @default.
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- W2750934433 title "Characterization of a novel whole blood model for the study of thrombin in complement activation and inflammation" @default.
- W2750934433 doi "https://doi.org/10.1016/j.molimm.2017.06.075" @default.
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