Open AccessNon-Lethal Endotoxin Injection: A Rat Model of Hypercoagulability
Author(s) -
Marjory B. Brooks,
James R. Turk,
Abraham Guerrero,
Padma K. Narayanan,
John P. Nolan,
Elizabeth G. Besteman,
Dennis W Wilson,
Roberta Thomas,
Cindy Fishman,
Karol L. Thompson,
Heidrun EllingerZiegelbauer,
Jennifer Pierson,
April Paulman,
Alan Y. Chiang,
A. Eric Schultze
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0169976
Subject(s) - inflammation , disseminated intravascular coagulation , fibrin , plasminogen activator inhibitor 1 , platelet , extracellular vesicle , coagulation , pharmacology , tissue plasminogen activator , immunology , medicine , systemic inflammation , tissue factor , thrombosis , platelet activation , intraperitoneal injection , plasminogen activator , microvesicles , chemistry , biochemistry , microrna , gene
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.