Abstract 218: Fibrinolytic Reactivity of Venous Endothelial Cells from Different Vascular Beds
Objective: Little is known about the molecular biology of endothelial cells from different venous vascular beds. As a result, our treatment of deep vein thrombosis (DVT) and pulmonary artery embolism (PE) remain identical. PAI-1 and tPA are important regulators of thrombosis and fibrinolysis, while ICAM-1 is known to bind fibrinogen. Here, we aim to investigate differences in fibrinolytic reactivity between human iliac vein endothelial cells (HIVECs) and human pulmonary artery endothelial cells (HPAECs).
Methods: Confluent HIVECs and HPAECs, passages 3 - 6, were cultured in the absence or presence of TNFα (10 ng/mL) for 24 hours. Cellular expression of tPA and PAI-1 as analyzed by Western blot analysis and ICAM-1 as analyzed by flow cytometry were compared to controls.
Results: Following TNFα stimulation, PAI-1 was upregulated in both HPAECs and HIVECs, however the upregulation observed in HPAECs was approximately 9-fold the increase observed in HIVECs (relative expression: 3.23 ± 0.52 vs 1.26 ± 0.27, n = 3, p < 0.05). While TNFα had no effect on tPA expression in HIVECs, tPA expression in HPAECS was upregulated by 33% (n = 3, p < 0.05). Although TNFα stimulation increased the number of ICAM-1 positive to approximately 100% in both cell types, a 3-fold greater increase in the Mean Fluorescence Intensity (MFI) was observed in HIVECs when compared to HPAECs (relative MFI: 69.28 ± 13.58 vs 21.92 ± 7.22, n = 3, p <0.05).
Conclusions: HPAECs and HIVECs react differently in terms of fibrinolytic potential when challenged with a cytokine associated with systemic inflammation, such as in DVT and PE. These findings suggest that endothelial cells from distinct venous vascular beds may differentially regulate the fibrinolytic pathway, thus demonstrating unique properties of the deep veins and the pulmonary artery to respond to thromboembolism.
- © 2012 by American Heart Association, Inc.