Inferior vena cava ligation rapidly induces tissue factor expression and venous thrombosis in rats.
OBJECTIVE
Although stasis is important in the pathogenesis of deep vein thrombosis (DVT), how it contributes to thrombogenesis is largely unknown. To gain mechanistic insight, we used a rat model of inferior vena cava (IVC) ligation.


RESULTS
Rats were subjected to IVC ligation for 15 to 60 minutes. Ligation resulted in rapid IVC dilatation and by 60 minutes, thrombi were detected in all rats. Small thrombi were detected in the IVC of most rats after 15 minutes of ligation. Thrombi were rich in fibrin, contained aggregated platelets as well as trapped leukocytes and red cells, and most originated at sites of localized endothelial denudation. Immunohistochemical analysis revealed tissue factor (TF)-expressing leukocytes within the thrombi and adherent to the vessel wall. Despite a largely intact vessel wall, endothelial cells also stained for TF. The expression of TF colocalized with that of protein disulfide isomerase (PDI), an enzyme implicated in TF decryption.


CONCLUSIONS
These findings suggest that the rapid development of DVT after IVC ligation reflects a combination of stasis-induced vein wall injury and enhanced TF expression in endothelial cells and leukocytes. Because TF expression occurs so soon after ligation, new synthesis is unlikely. Instead, stasis-induced venous dilatation with or without exposure of subendothelial TF, may be responsible for vessel wall TF expression. Colocalization of TF and PDI raises the possibility that PDI-mediated TF decryption plays a role in the pathogenesis of DVT.
Zhou
Ji
J
Department of Medicine, McMaster University, Hamilton, Ontario, Canada. jzhou@thrombosis.hhscr.org
May
Linda
L
Liao
Peng
P
Gross
Peter L
PL
Weitz
Jeffrey I
JI
D000818:Animals; D002448:Cell Adhesion; D004108:Dilatation, Pathologic; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D008026:Ligation; D019007:P-Selectin / Q000378:metabolism; D019704:Protein Disulfide-Isomerases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013925:Thromboplastin / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation; D014682:Vena Cava, Inferior / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D020246:Venous Thrombosis / Q000378:metabolism* / Q000473:pathology
D019007:P-Selectin; D013925:Thromboplastin; D019704:Protein Disulfide-Isomerases