Non-lethal endotoxin injection: A rat model of hypercoagulability

Marjory B. Brooks, James R. Turk, Abraham Guerrero, Padma K. Narayanan, John P. Nolan, Elizabeth G. Besteman, Dennis W Wilson, Roberta A. Thomas, Cindy E. Fishman, Karol L. Thompson, Heidrun Ellinger-Ziegelbauer, Jennifer B. Pierson, April Paulman, Alan Y. Chiang, Albert E. Schultze

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Systemic inflammation co-activates coagulation, which unchecked culminates in a lethal syndrome of multi-organ microvascular thrombosis known as disseminated intravascular coagulation (DIC). We studied an endotoxin-induced inflammatory state in rats to identify biomarkers of hemostatic imbalance favoring hypercoagulability. Intraperitoneal injection of LPS at 15 mg/kg body weight resulted in peripheral leukopenia and widespread neutrophilic sequestration characteristic of an acute systemic inflammatory response. Early indicators of hemostatic pathway activation developed within 4 hours, including increased circulating concentrations of procoagulant extracellular vesicles (EVs), EVs expressing endothelial cell and platelet membrane markers, and high concentration of soluble intercellular adhesion molecule-1 (sICAM-1), plasminogen activator inhibitor-1 (PAI-1), and D-dimers. Inflammation persisted throughout the 48-hour observation period; however, increases were found in a subset of serum microRNA (miRNA) that coincided with gradual resolution of hemostatic protein abnormalities and reduction in EV counts. Dose-adjusted LPS treatment in rats provides a time-course model to develop biomarker profiles reflecting procoagulant imbalance and rebalance under inflammatory conditions.

Original languageEnglish (US)
Article numbere0169976
JournalPLoS One
Volume12
Issue number1
DOIs
StatePublished - Jan 1 2017

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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    Brooks, M. B., Turk, J. R., Guerrero, A., Narayanan, P. K., Nolan, J. P., Besteman, E. G., Wilson, D. W., Thomas, R. A., Fishman, C. E., Thompson, K. L., Ellinger-Ziegelbauer, H., Pierson, J. B., Paulman, A., Chiang, A. Y., & Schultze, A. E. (2017). Non-lethal endotoxin injection: A rat model of hypercoagulability. PLoS One, 12(1), [e0169976]. https://doi.org/10.1371/journal.pone.0169976