Role of the protein C pathway in the extraintestinal thrombosis associated with murine colitis.
OBJECTIVE
Chronic inflammatory bowel diseases (IBD) are associated with an increased risk for thromboembolism. Although thrombosis is known to contribute to the morbidity and mortality of patients with IBD, the underlying mechanisms that contribute to the genesis of a hypercoagulable state during intestinal inflammation remain poorly defined. The objective of this study was to determine whether the protein C pathway contributes to the enhanced extraintestinal thrombosis that is associated with dextran sodium sulfate (DSS)-induced colitis in mice.


METHODS
Microvascular thrombosis was induced in cremaster muscle microvessels of normal and colitic mice using a light/dye injury model. DSS colitis enhanced thrombus formation in cremaster arterioles of wild-type mice.


RESULTS
The DSS-induced thrombosis response was greatly attenuated in transgenic mice over expressing the endothelial protein C receptor. Activated protein C (APC), administered to colitic WT mice immediately prior to photoactivation, also afforded protection against thrombosis, and an anti-APC antibody enhanced thrombus formation.


CONCLUSIONS
These findings indicate that elevated APC levels, derived from either endogenous or exogenous sources, confer protection against the extraintestinal thrombosis that accompanies colonic inflammation.
Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130-33932, USA.
Hideo
H
Yoshida
Janice
J
Russell
Karen Y
KY
Stokes
Cigdem Erkuran
CE
Yilmaz
Charles T
CT
Esmon
D Neil
DN
Granger
D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000150:complications*; D016264:Dextran Sulfate; D004730:Endothelium, Vascular / Q000378:metabolism; D018056:Hemorheology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000098:blood supply; D011486:Protein C / Q000378:metabolism / Q000502:physiology*; D013927:Thrombosis / Q000503:physiopathology*
D011486:Protein C; D016264:Dextran Sulfate