Induction of heme oxygenase-1 is a beneficial response in a murine model of venous thrombosis

Michal J. Tracz, Julio P. Juncos, Joseph P. Grande, Anthony J. Croatt, Allan W. Ackerman, Zvonimir S. Katusic, Karl A. Nath

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

The induction of heme oxygenase-1 (HO-1) may protect against tissue injury. The present study examines the induction of HO-1 in a murine model of venous thrombosis and explores the downstream consequences of this induction. In a model of stasis-induced thrombosis created by ligation of the inferior vena cava, HO-1 expression is markedly induced. Such expression occurs primarily in smooth muscle cells in the venous wall and in leukocytes infiltrating the venous wall and clot. To determine the significance of HO-1 induction in venous thrombosis, this model was imposed in HO-1+/+ and HO-1-/- mice. The initial clot size did not differ in either group by day 2, but was significantly larger in HO-1-/- mice by day 10, where an exaggerated inflammatory response in the venous wall was also observed. Following ligation of the inferior vena cava, HO-1-/- mice exhibited increased nuclear factor κB activation and markedly increased up-regulation of tissue factor, selectins, inflammatory cytokines, and matrix metalloproteinase-9, the latter incriminated in both clot lysis and vascular injury. We conclude that HO-1 deficiency impairs thrombus resolution and exaggerates the inflammatory response to thrombus formation. These findings offer insight into recent observations that polymorphisms in the HO-1 gene may increase the risk for recurrent venous thrombosis and dysfunction of hemodialysis arteriovenous fistulas, the latter caused, in part, by thrombosis.

Original languageEnglish (US)
Pages (from-to)1882-1890
Number of pages9
JournalAmerican Journal of Pathology
Volume173
Issue number6
DOIs
StatePublished - Dec 2008

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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