Abstract 345: The Thrombotic Reactivity of Endothelial Cells from Deep Vein and Pulmonary Artery Venous Beds in Response to Thrombin
Background Pulmonary embolism (PE) is thought to occur largely due to deep venous thrombosis from the lower extremities. A portion of PEs however may result from primary pulmonary artery thrombosis. Recent studies have shown pulmonary artery endothelial cells have increased fibrinolytic reactivity compared to iliac vein endothelial cells in response to TNFα stimulation, a cytokine known to be up-regulated in the systemic response to trauma. The goal of this study was to determine if similar thrombotic stimuli occurs in non-trauma situations.
Methods Human iliac vein endothelial cells (HIVEC) and human pulmonary artery endothelial cells (HPAEC) were incubated at 37° C in the presence or absence of 25pM thrombin for 24 hours. Plasminogen activator inhibitor-1 (PAI-1), uPA, tPA, EPCR, PAR-1 and TM expression in cell lysates were evaluated by Western blot analysis. ICAM-1 cell surface expression was evaluated by flow cytometry.
Results While thrombin had no effect on the expression of uPA in HPAEC, there was a ~15% decrease in expression in HIVEC. With tPA, HPAEC and HIVEC had an 11% and ~25% increase in expression, respectively. In contrast, thrombin stimulation caused a decrease in PAI-1 expression in HPAEC while having no effect on HIVEC. There was no change in EPCR expression in HPAEC, however there was a 22% decrease in HIVEC. HPAEC demonstrated decreased expression of PAR1, in contrast to an almost 40% increase in PAR1 expression in HIVEC. Thrombin produced no change in HIVEC recombinant TM expression, however, 11% increase in expression was observed in HPAEC. With ICAM-1, neither HIVEC nor HPAEC had a change in expression after thrombin stimulation.
Conclusion This data shows that endothelium of the deep veins reacts differently from pulmonary arterial endothelium in response to non-trauma stimuli. Endothelial cells from the iliac vein and pulmonary artery venous beds differentially express markers of the fibrinolytic and coagulation pathways, and this variance in expression may play a role in the thrombotic reactivity of these vascular beds.
- © 2013 by American Heart Association, Inc.