Chatterjee2010_BloodCoagulation

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This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
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To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

Format
SBML (L2V4)
Related Publication
  • Systems biology of coagulation initiation: kinetics of thrombin generation in resting and activated human blood.
  • Chatterjee MS, Denney WS, Jing H, Diamond SL
  • PLoS computational biology , 9/ 2010 , Volume 6
  • Department of Chemical and Biomolecular Engineering, Institute for Medicine and Engineering, University of Pennsylvania. Philadelphia, Pennslyvania, United States of America.
  • Blood function defines bleeding and clotting risks and dictates approaches for clinical intervention. Independent of adding exogenous tissue factor (TF), human blood treated in vitro with corn trypsin inhibitor (CTI, to block Factor XIIa) will generate thrombin after an initiation time (T(i)) of 1 to 2 hours (depending on donor), while activation of platelets with the GPVI-activator convulxin reduces T(i) to ∼20 minutes. Since current kinetic models fail to generate thrombin in the absence of added TF, we implemented a Platelet-Plasma ODE model accounting for: the Hockin-Mann protease reaction network, thrombin-dependent display of platelet phosphatidylserine, VIIa function on activated platelets, XIIa and XIa generation and function, competitive thrombin substrates (fluorogenic detector and fibrinogen), and thrombin consumption during fibrin polymerization. The kinetic model consisting of 76 ordinary differential equations (76 species, 57 reactions, 105 kinetic parameters) predicted the clotting of resting and convulxin-activated human blood as well as predicted T(i) of human blood under 50 different initial conditions that titrated increasing levels of TF, Xa, Va, XIa, IXa, and VIIa. Experiments with combined anti-XI and anti-XII antibodies prevented thrombin production, demonstrating that a leak of XIIa past saturating amounts of CTI (and not "blood-borne TF" alone) was responsible for in vitro initiation without added TF. Clotting was not blocked by antibodies used individually against TF, VII/VIIa, P-selectin, GPIb, protein disulfide isomerase, cathepsin G, nor blocked by the ribosome inhibitor puromycin, the Clk1 kinase inhibitor Tg003, or inhibited VIIa (VIIai). This is the first model to predict the observed behavior of CTI-treated human blood, either resting or stimulated with platelet activators. CTI-treated human blood will clot in vitro due to the combined activity of XIIa and XIa, a process enhanced by platelet activators and which proceeds in the absence of any evidence for kinetically significant blood borne tissue factor.
Contributors
Michael Schubert

Metadata information

is
BioModels Database MODEL1108260014
isDescribedBy
PubMed 20941387
hasProperty
Mathematical Modelling Ontology Ordinary differential equation model
Curation status
Non-curated
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  • Model originally submitted by : Michael Schubert
  • Submitted: Aug 26, 2011 5:52:21 PM
  • Last Modified: Aug 29, 2011 3:38:55 PM
Revisions
  • Version: 2 public model Download this version
    • Submitted on: Aug 29, 2011 3:38:55 PM
    • Submitted by: Michael Schubert
    • With comment: Current version of Chatterjee2010_BloodCoagulation
  • Version: 1 public model Download this version
    • Submitted on: Aug 26, 2011 5:52:21 PM
    • Submitted by: Michael Schubert
    • With comment: Original import of Chatterjee 2010