Skip to main content
Log in

A Computational Analysis of FXa Generation by TF:FVIIa on the Surface of Rat Vascular Smooth Muscle Cells

  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

A computational model was developed to investigate the contribution of classical mass transport and flow parameters to factor X (FX) activation by the tissue factor–factor VIIa complex (TF:VIIa) on one wall of a parallel-plate flow chamber. The computational results were compared to previously obtained experimental data for the generation of factor Xa (FXa) by TF:VIIa on the surface of cultured rat vascular smooth muscle cells. In this study, the complete steady-state convection–diffusion equation was solved using the commercial software package, FLUENT (Fluent Inc., Lebanon, New Hampshire). A user-defined subroutine interfaced with FLUENT implemented the surface reaction which was modeled using classical Michaelis–Menten reaction kinetics. The numerical solutions were obtained for 12 cases which used combinations of three wall shear rates and four reaction rates. The numerically obtained fluxes for a given reaction rate displayed a wall shear rate dependence which ranged from classical kinetic reaction control (no dependence) to pure diffusional control (maximum dependence). The experimental data, however, were not represented by numerical data generated using a single reaction rate. The three numerically obtained fluxes which corresponded most closely to the experimental fluxes were determined using three different V max values. This finding supports the hypothesis that there may be a direct effect of flow on the TF:VIIa complex or the cell membrane. © 1998 Biomedical Engineering Society.

PAC98: 8722-q, 8710+e

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

REFERENCES

  1. Bird, R. B., W. E. Stewart, and E. N. Lightfoot. Transport Phenomena. New York: Wiley, 1960, pp. 513 and 514.

    Google Scholar 

  2. Bloem, L. J., L. Chen, W. H. Konigsberg, and R. Bach. Serum stimulation of quiescent human fibroblasts induces the synthesis of tissue factor mRNA followed by the appearance of tissue factor antigen and procoagulant activity. J. Cell Physiol.139:418-423, 1989.

    Google Scholar 

  3. Darnell, J., H. Lodish, and D. Baltimore. Molecular Cell Biology. New York: Scientific American, 1990, pp. 61 and 62.

    Google Scholar 

  4. Fluent Manual Series. User's Guide, Vols. 1-4, Fluent Inc., Lebanon, New Hampshire, 1995.

  5. Gemmel, C. H., Y. Nemerson, and V. T. Turitto. The effects of shear rate on the enzymatic activity of the tissue factor- factor VIIa complex. Microvasc. Res.40:327-340, 1990.

    Google Scholar 

  6. Gemmel, C. H., V. T. Turitto, and Y. Nemerson. Flow as a regulator of the activation of factor Xby tissue factor. Blood72:1404-1406, 1988.

    Google Scholar 

  7. Gir, S., S. M. Slack, and V. T. Turitto. A numerical analysis of factor X activation in the presence of tissue factor-factor VIIa complex in a flow reactor. Ann. Biomed. Eng.24:394- 399, 1996.

    Google Scholar 

  8. Goldsmith, H. L., and V. T. Turitto. Rheological aspects of thrombosis and haemostasis: Basic principles and applications. Thromb. Haemost. 55:415-435, 1986.

    Google Scholar 

  9. Grabowski, E. F., D. B. Zuckerman, and Y. Nemerson. The functional expression of tissue factor by fibroblasts and endothelial cells under flow conditions. Blood81:3265-3270, 1993.

    Google Scholar 

  10. Hall, C. L. The Effects of Flow on Tissue Factor Activity in Rat Vascular Smooth Muscle Cells. Ph.D. dissertation, The University of Memphis, 1995.

  11. Ichinose, A., and W. Davie. The blood coagulation factors: Their cDNAs, genes and expression. In: Hemostasis and Thrombosis: Basic Principles and Clinical Practice, edited by R. W. Colman, J. Hirsh, V. J. Marder, and E. W. Salzman. Philadelphia: Lippincott, 1994, pp. 19-54.

    Google Scholar 

  12. Leveque, M. A. Les trois de la transmission de chaleur par convection. Ann. Mines13:211-239, 1928.

    Google Scholar 

  13. Levich, V. G. Physicochemical Hydrodynamics. Englewood Cliffs, NJ: Prentice-Hall, 1962, pp. 39-138.

    Google Scholar 

  14. Maynard, J. R., B. E. Dreyer, M. B. Stemerman, and F. Pitlick. Tissue-factor coagulant activity of cultured human endothelial and smooth muscle cells and fibroblasts. Blood50:387-396, 1977.

    Google Scholar 

  15. Miletich, J. P., G. Broze, Jr., and P. W. Majerus. Purification of human coagulation factors II, IX, and X using sulfated dextran beads. Methods Enzymol.80:221-228, 1981.

    Google Scholar 

  16. Nemerson, Y. Tissue factor and hemostasis. Blood71:1-8, 1988.

    Google Scholar 

  17. Nemerson, Y. Tissue factor pathway of coagulation. In: Hemostasis and Thrombosis: Basic Principles and Clinical Practice, edited by R. W. Colman, J. Hirsh, V. J. Marder, and E. W. Salzman. Philadelphia PA: Lippincott, 1994, pp. 81-93.

    Google Scholar 

  18. Nemerson, Y., and R. Gentry. An ordered addition, essential activation model of the tissue factor pathway of coagulation: Evidence for a conformational cage. Biochemistry25:4020- 4033, 1986.

    Google Scholar 

  19. Patankar, S. V. Numerical Heat Transfer and Fluid Flow. New York: Hemisphere, 1980, pp. 160-162.

    Google Scholar 

  20. Slack, S. M., Y. Cui, and V. T. Turitto. The effects of flow on blood coagulation and thrombosis. Thromb. Haemost.70:129-134, 1993.

    Google Scholar 

  21. Slack, S. M., and V. T. Turitto. Fluid dynamic and hemorheologic considerations. Cardiovasc. Pathol.2:11S- 21S, 1993.

    Google Scholar 

  22. Stenflo, J., and B. Dahlback. Vitamin K-dependent proteins. In: The Molecular Basis of Blood Diseases, edited by G. Stamatoyannopoulos, A. W. Nienhuis, P. W. Majerus, and H. Varmus. Philadelphia: Saunders, 1994, pp. 565-598.

    Google Scholar 

  23. Taubman, M. B., J. Marmur, C.-L. Rosenfield, A. Guha, S. Nichtburger, and Y. Nemerson. Agonist-mediated tissue factor expression in cultured vascular smooth muscle cells: Role of Ca2+ mobilization and protein kinase C activation. J. Clin. Invest.91:547-552, 1993.

    Google Scholar 

  24. Versteeg, H. K., and W. Malalasekera. An Introduction to Computational Fluid Dynamics: The Finite Volume Method. Harlow, Essex, England: Longman Scientific and Technical, 1995.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hall, C.L., Slack, S.M. & Turitto, V.T. A Computational Analysis of FXa Generation by TF:FVIIa on the Surface of Rat Vascular Smooth Muscle Cells. Annals of Biomedical Engineering 26, 28–36 (1998). https://doi.org/10.1114/1.120

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1114/1.120

Navigation