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

6 Citations (Scopus)

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

Fingerprint

Thrombophilia
Hemostatics
endotoxins
Endotoxins
Rats
inflammation
animal models
Biomarkers
injection
Coagulation
Injections
biomarkers
Inflammation
disseminated intravascular coagulation
leukopenia
Disseminated Intravascular Coagulation
thrombosis
Plasminogen Activator Inhibitor 1
rats
Endothelial cells

ASJC Scopus subject areas

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

Cite this

Brooks, M. B., Turk, J. R., Guerrero, A., Narayanan, P. K., Nolan, J. P., Besteman, E. G., ... 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

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

In: PLoS One, Vol. 12, No. 1, e0169976, 01.01.2017.

Research output: Contribution to journalArticle

Brooks, MB, Turk, JR, Guerrero, A, Narayanan, PK, Nolan, JP, Besteman, EG, Wilson, DW, Thomas, RA, Fishman, CE, Thompson, KL, Ellinger-Ziegelbauer, H, Pierson, JB, Paulman, A, Chiang, AY & Schultze, AE 2017, 'Non-lethal endotoxin injection: A rat model of hypercoagulability', PLoS One, vol. 12, no. 1, e0169976. https://doi.org/10.1371/journal.pone.0169976
Brooks MB, Turk JR, Guerrero A, Narayanan PK, Nolan JP, Besteman EG et al. Non-lethal endotoxin injection: A rat model of hypercoagulability. PLoS One. 2017 Jan 1;12(1). e0169976. https://doi.org/10.1371/journal.pone.0169976
Brooks, Marjory B. ; Turk, James R. ; Guerrero, Abraham ; Narayanan, Padma K. ; Nolan, John P. ; Besteman, Elizabeth G. ; Wilson, Dennis W ; Thomas, Roberta A. ; Fishman, Cindy E. ; Thompson, Karol L. ; Ellinger-Ziegelbauer, Heidrun ; Pierson, Jennifer B. ; Paulman, April ; Chiang, Alan Y. ; Schultze, Albert E. / Non-lethal endotoxin injection : A rat model of hypercoagulability. In: PLoS One. 2017 ; Vol. 12, No. 1.
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