Increased thrombosis after arterial injury in human C-reactive protein-transgenic mice.
BACKGROUND
C-reactive protein (CRP), an acute-phase reactant long considered merely an innocent bystander in the inflammatory process, is now recognized as a powerful predictor of cardiovascular events. Emerging in vitro evidence suggests that CRP may have direct proinflammatory and prothrombotic effects on monocytes and endothelial cells. To determine whether CRP directly modulates vascular cell function in vivo, we subjected wild-type mice, which do not express CRP, and human CRP-transgenic (CRPtg) mice to 2 models of arterial injury.


RESULTS
Baseline serum CRP levels in CRPtg mice were 18+/-6 mg/L. CRP levels were undetectable in wild-type mice. Transluminal wire injury led to complete thrombotic occlusion of the femoral artery at 28 days in 75% of CRPtg arteries (6 of 8) compared with 17% (2 of 12) in wild-type mice (P<0.05). In a model of arterial photochemical injury, clot formation time was shortened in CRPtg mice; mean time to occlusion was 33+/-19 minutes compared with 59+/-19 minutes in wild-type mice (n=10; P<0.05).


CONCLUSIONS
Arterial injury in CRPtg mice results in an expedited and higher rate of thrombotic occlusion. This is the first report of a prothrombotic phenotype directly attributable to the presence of human CRP in vivo. Investigation of the inflammatory-thrombotic axis in CRPtg mice may elucidate the prothrombotic actions of CRP in unstable arterial diseases and may pave the way for novel therapeutic interventions for preventing cardiovascular events.
Danenberg
Haim D
HD
Harvard-MIT Division of Health Sciences and Technology, Cambridge, Mass 02139, USA. danen@mit.edu
Szalai
Alexander J
AJ
Swaminathan
Rajesh V
RV
Peng
Lin
L
Chen
Zhiping
Z
Seifert
Philip
P
Fay
William P
WP
Simon
Daniel I
DI
Edelman
Elazer R
ER
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D002097:C-Reactive Protein / Q000235:genetics* / Q000378:metabolism; D017536:Carotid Artery, Common / Q000187:drug effects* / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D005263:Femoral Artery / Q000293:injuries* / Q000473:pathology; D020022:Genetic Predisposition to Disease; D006801:Humans; D007834:Lasers; D007958:Leukocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D010777:Photochemistry; D010976:Platelet Count; D012395:Rose Bengal; D013927:Thrombosis / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology
D012395:Rose Bengal; D002097:C-Reactive Protein