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 language | English (US) |
|---|---|
| Article number | e0169976 |
| Journal | PLoS One |
| Volume | 12 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2017 |
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ASJC Scopus subject areas
- Medicine(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Agricultural and Biological Sciences(all)
Cite this
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 journal › Article
}
TY - JOUR
T1 - Non-lethal endotoxin injection
T2 - A rat model of hypercoagulability
AU - Brooks, Marjory B.
AU - Turk, James R.
AU - Guerrero, Abraham
AU - Narayanan, Padma K.
AU - Nolan, John P.
AU - Besteman, Elizabeth G.
AU - Wilson, Dennis W
AU - Thomas, Roberta A.
AU - Fishman, Cindy E.
AU - Thompson, Karol L.
AU - Ellinger-Ziegelbauer, Heidrun
AU - Pierson, Jennifer B.
AU - Paulman, April
AU - Chiang, Alan Y.
AU - Schultze, Albert E.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85009386870&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85009386870&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0169976
DO - 10.1371/journal.pone.0169976
M3 - Article
C2 - 28081568
AN - SCOPUS:85009386870
VL - 12
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 1
M1 - e0169976
ER -