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

Francis J. Castellino; Jorge G. Ganopolsky; Francisco Noria; Mayra J. Sandoval-Cooper; Victoria A. Ploplis

doi:10.1160/TH06-08-0430

Thrombosis and Haemostasis, Table of Contents

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

Authors

Francis J. Castellino

¹W. M. Keck Center for Transgene Research and Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA
Jorge G. Ganopolsky

¹W. M. Keck Center for Transgene Research and Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA
Francisco Noria

¹W. M. Keck Center for Transgene Research and Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA
Mayra J. Sandoval-Cooper

¹W. M. Keck Center for Transgene Research and Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA
Victoria A. Ploplis

¹W. M. Keck Center for Transgene Research and Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA

Abstract

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

Full Text

References

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