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Thromb Haemost 2006; 96(06): 794-801
DOI: 10.1160/TH06-08-0430
Wound Healing and Inflammation/Infection
Schattauer GmbH

Focal arterial inflammation is augmented in mice with a deficiency of the protein C gene

Francis J. Castellino
1   W. M. Keck Center for Transgene Research and Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA
,
Jorge G. Ganopolsky
1   W. M. Keck Center for Transgene Research and Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA
,
Francisco Noria
1   W. M. Keck Center for Transgene Research and Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA
,
Mayra J. Sandoval-Cooper
1   W. M. Keck Center for Transgene Research and Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA
,
Victoria A. Ploplis
1   W. M. Keck Center for Transgene Research and Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA
› Author AffiliationsFinancial support: This work was supported by grants HL019982 and HL073750 (to FJC) from the National Institutes of Health, and the Kleiderer-Pezold professorship (to FJC).
Further Information

Publication History

Received 05 August 2006

Accepted after revision 28 October 2006

Publication Date:
29 November 2017 (online)

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Summary

Increased risk of thrombosis, with propitious conditions for fibrin deposition, along with upregulation of inflammation, are important factors that enhance plaque formation in atherosclerosis. Evidence supporting the role of anticoagulant protein C (PC) as an inflammatory agent has emerged, supplementing its wellknown function as an anticoagulant. Thus, we sought to examine whethera PC deficiency would lead to an enhanced response to an acute arterial hyperplasic challenge. The presentation of early arterial inflammation was studied using a copper/silicone arterial cuff model of accelerated focal neointimal remodeling in mice with a heterozygous total deficiency of PC (PC+/−). Increased inflammation, cell proliferation, cell migration, fibrin elevation, and tissue necrosis were observed in the treated arteries of PC+/−mice, as compared to arteries of equally challenged age- and gender-matched WT mice. These results indicate that PC+/−mice subjected to this challenge displayed enhanced focal arterial inflammation and thrombosis, leading to larger neointimas and subsequent localized occlusion, as compared to their WT counterparts.

Keywords

Inflammation - thrombosis - arterial injury - arterial remodeling - arterial neointima formation

Footnote:

J.G.G., M.J.S-C., and F.N. contributed equally to the performance of the experiments.


 

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