Impact of Serum Amyloid A on Tissue Factor and Tissue Factor Pathway Inhibitor Expression and Activity in Endothelial Cells

Abstract

Objective— Although serum amyloid A (SAA) is a useful biomarker of coronary artery disease (CAD), its direct role in procoagulation is obscure. This study investigates the impact of SAA on the expression and activity of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in endothelial cells. Methods and Results— SAA was found to disturb the balance of TF and TFPI expression and activity in human endothelial cells. SAA (20 μg/mL) markedly induced TF expression between 4 to 8 hours in both protein and mRNA levels, as well as TF activity. Conversely, incubation of SAA (20 μg/mL) for 24 and 48 hours was found to significantly inhibit TFPI secretion, transcription, and activity. Pretreatment with formyl peptide receptor-like 1 (FPRL1) inhibitors (Pertussis toxin and WRWWWW) could block the SAA effects on TF and TFPI. Furthermore, pretreatment with the respective specific mitogen-activated protein kinase (MAPK) inhibitors (SB203580, PD98059, and SP600125) and NFκB inhibitor (Bay-11 to 7082) could block SAA-dependent TF induction. SAA also directly induced activation of MAP kinases and NFκB. Conclusions— The stimulating effect of SAA was faster-acting on the expression and activity of TF and the inhibitory effect was slower-acting on TFPI. The effects are mediated through FPRL1, MAP kinases and NFκB.