Display options
Cite
Zilberman-Rudenko J, Itakura A, Maddala J, et al. Biorheology of platelet activation in the bloodstream distal to thrombus formation. Cell Mol Bioeng. 2016;9(4):496-508doi: 10.1007/s12195-016-0448-5.
Zilberman-Rudenko, J., Itakura, A., Maddala, J., Baker-Groberg, S. M., Vetter, R., Tucker, E. I., Gruber, A., Gerdes, C., & McCarty, O. J. (2016). Biorheology of platelet activation in the bloodstream distal to thrombus formation. Cellular and molecular bioengineering, 9(4), 496-508. https://doi.org/10.1007/s12195-016-0448-5
Zilberman-Rudenko, Jevgenia, et al. "Biorheology of platelet activation in the bloodstream distal to thrombus formation." Cellular and molecular bioengineering vol. 9,4 (2016): 496-508. doi: https://doi.org/10.1007/s12195-016-0448-5
Zilberman-Rudenko J, Itakura A, Maddala J, Baker-Groberg SM, Vetter R, Tucker EI, Gruber A, Gerdes C, McCarty OJ. Biorheology of platelet activation in the bloodstream distal to thrombus formation. Cell Mol Bioeng. 2016 Dec;9(4):496-508. doi: 10.1007/s12195-016-0448-5. Epub 2016 May 26. PMID: 28083075; PMCID: PMC5221751.
Copy Download .nbib Format: NLM
Share it on

Cell Mol Bioeng. 2016 Dec;9(4):496-508. doi: 10.1007/s12195-016-0448-5. Epub 2016 May 26.

Biorheology of platelet activation in the bloodstream distal to thrombus formation.

Cellular and molecular bioengineering

Jevgenia Zilberman-Rudenko, Asako Itakura, Jeevan Maddala, Sandra M Baker-Groberg, Ralf Vetter, Erik I Tucker, András Gruber, Christoph Gerdes, Owen J T McCarty

Affiliations

  1. Department of Biomedical Engineering, School of Medicine, Oregon Health & Science University, 3303 SW Bond Ave, Portland, OR, USA.
  2. Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, USA; Drug Discovery, Bayer Pharma AG, Wuppertal, Germany.
  3. Department of Biomedical Engineering, School of Medicine, Oregon Health & Science University, 3303 SW Bond Ave, Portland, OR, USA; Chemical and Biomedical Engineering, West Virginia University, Morgantown, WV.
  4. Drug Discovery, Bayer Pharma AG, Wuppertal, Germany.
  5. Department of Biomedical Engineering, School of Medicine, Oregon Health & Science University, 3303 SW Bond Ave, Portland, OR, USA; Division of Hematology / Medical Oncology, School of Medicine, Oregon Health & Science University, Portland, OR, USA.
  6. Department of Biomedical Engineering, School of Medicine, Oregon Health & Science University, 3303 SW Bond Ave, Portland, OR, USA; Division of Hematology / Medical Oncology, School of Medicine, Oregon Health & Science University, Portland, OR, USA; Aronora Inc., Portland, OR, USA.
  7. Department of Biomedical Engineering, School of Medicine, Oregon Health & Science University, 3303 SW Bond Ave, Portland, OR, USA; Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, USA; Division of Hematology / Medical Oncology, School of Medicine, Oregon Health & Science University, Portland, OR, USA.

PMID: 28083075 PMCID: PMC5221751 DOI: 10.1007/s12195-016-0448-5

Abstract

Thrombus growth at the site of vascular injury is mediated by the sequential events of platelet recruitment, activation and aggregation concomitant with the initiation of the coagulation cascade, resulting in local thrombin generation and fibrin formation. While the biorheology of a localized thrombus formation has been well studied, it is unclear whether local sites of thrombin generation propagate platelet activation within the bloodstream. In order to study the physical biology of platelet activation downstream of sites of thrombus formation, we developed a platform to measure platelet activation and microaggregate formation in the bloodstream. Our results show that thrombi formed on collagen and tissue factor promote activation and aggregation of platelets in the bloodstream in a convection-dependent manner. Pharmacological inhibition of the coagulation factors (F) X, XI or thrombin dramatically reduced the degree of distal platelet activation and microaggregate formation in the bloodstream without affecting the degree of local platelet deposition and aggregation on a surface of immobilized collagen. Herein we describe the development and an example of the utility of a platform to study platelet activation and microaggregate formation in the bloodstream (convection-limited regime) relative to the local site of thrombus formation.

Keywords: biophysics; factor X; factor XI; physical biology; platelets; shear; thrombin

References

  1. Front Oncol. 2012 Sep 14;2:108 - PubMed
  2. Haemophilia. 2014 May;20 Suppl 4:50-3 - PubMed
  3. Eur J Biochem. 1985 Sep 2;151(2):217-24 - PubMed
  4. Annu Rev Fluid Mech. 2015 Jan 1;47:377-403 - PubMed
  5. Blood. 2012 Dec 20;120(26):5209-16 - PubMed
  6. Cell Mol Bioeng. 2014 Mar;7(1):1-14 - PubMed
  7. Arterioscler Thromb Vasc Biol. 2001 Jan;21(1):149-56 - PubMed
  8. J Leukoc Biol. 2011 Nov;90(5):923-7 - PubMed
  9. Cell Mol Bioeng. 2014 Jun 1;7(2):285-290 - PubMed
  10. Phys Biol. 2011 Dec;8(6):066005 - PubMed
  11. Methods Mol Med. 2004;93:21-34 - PubMed
  12. Blood. 2010 Nov 11;116(19):3981-9 - PubMed
  13. J Med Chem. 2005 Sep 22;48(19):5900-8 - PubMed
  14. Arterioscler Thromb Vasc Biol. 2006 Aug;26(8):1729-37 - PubMed
  15. J Biol Chem. 1992 Sep 25;267(27):19691-7 - PubMed
  16. J Cardiovasc Pharmacol. 2002 Apr;39(4):552-60 - PubMed
  17. J Thromb Haemost. 2016 Mar;14 (3):619-22 - PubMed
  18. Blood. 2009 Jul 9;114(2):452-8 - PubMed
  19. J Thromb Haemost. 2010 Jun;8(6):1295-301 - PubMed
  20. Arterioscler Thromb Vasc Biol. 2016 Mar;36(3):510-7 - PubMed
  21. J Thromb Haemost. 2013 Jul;11(7):1341-52 - PubMed
  22. Cell Mol Bioeng. 2012 Dec;5(4):488-492 - PubMed
  23. Thromb Res. 2004;114(5-6):447-53 - PubMed

Publication Types

Grant support