Non-Lethal Endotoxin Injection: A Rat Model of Hypercoagulability.
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 fav...
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doaj-d1a2148f4656495f9cebe693e28738c62020-11-25T02:32:11ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01121e016997610.1371/journal.pone.0169976Non-Lethal Endotoxin Injection: A Rat Model of Hypercoagulability.Marjory B BrooksJames R TurkAbraham GuerreroPadma K NarayananJohn P NolanElizabeth G BestemanDennis W WilsonRoberta A ThomasCindy E FishmanKarol L ThompsonHeidrun Ellinger-ZiegelbauerJennifer B PiersonApril PaulmanAlan Y ChiangAlbert E SchultzeSystemic 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.http://europepmc.org/articles/PMC5233421?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Non-Lethal Endotoxin Injection: A Rat Model of Hypercoagulability. PLoS ONE |
author_facet |
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 |
author_sort |
Marjory B Brooks |
title |
Non-Lethal Endotoxin Injection: A Rat Model of Hypercoagulability. |
title_short |
Non-Lethal Endotoxin Injection: A Rat Model of Hypercoagulability. |
title_full |
Non-Lethal Endotoxin Injection: A Rat Model of Hypercoagulability. |
title_fullStr |
Non-Lethal Endotoxin Injection: A Rat Model of Hypercoagulability. |
title_full_unstemmed |
Non-Lethal Endotoxin Injection: A Rat Model of Hypercoagulability. |
title_sort |
non-lethal endotoxin injection: a rat model of hypercoagulability. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2017-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC5233421?pdf=render |
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