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Updated: Jul 15, 2026
Extracellular Vesicle Tissue Factor Activity Assay
Published on: December 29, 2023
Impact of serum amyloid A on tissue factor and tissue factor pathway inhibitor expression and activity in endothelial
Yulan Zhao1, Shuli Zhou, Chew-Kiat Heng
1Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, 5, Lower Kent Ridge Rd, Singapore 119074.
Insights
Serum amyloid A (SAA) impacts blood clotting by increasing tissue factor (TF) and decreasing tissue factor pathway inhibitor (TFPI) in endothelial cells. These effects are mediated by FPRL1, MAP kinases, and NF-kappaB signaling pathways.
Area of Science:
- Biochemistry
- Molecular Biology
- Cardiovascular Research
Background:
- Serum amyloid A (SAA) is a known biomarker for coronary artery disease (CAD).
- The precise role of SAA in procoagulation, particularly its effects on key regulatory proteins, remains unclear.
Purpose of the Study:
- To investigate the influence of SAA on the expression and activity of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in human endothelial cells.
- To elucidate the signaling pathways involved in SAA-mediated regulation of TF and TFPI.
Main Methods:
- Human endothelial cells were treated with SAA (20 microg/mL).
- TF and TFPI expression (mRNA and protein) and activity were measured at various time points.
- Cells were pretreated with inhibitors of formyl peptide receptor-like 1 (FPRL1), mitogen-activated protein kinases (MAPKs), and NF-kappaB.
- Activation of MAPKs and NF-kappaB by SAA was assessed.
Main Results:
- SAA rapidly induced TF expression and activity within 4-8 hours.
- SAA significantly inhibited TFPI secretion, transcription, and activity after 24-48 hours.
- FPRL1, MAPK, and NF-kappaB signaling pathways were identified as mediators of SAA's effects on TF and TFPI.
Conclusions:
- SAA differentially regulates TF and TFPI, promoting a procoagulant state in endothelial cells.
- The observed effects are mediated through the FPRL1 receptor and downstream signaling involving MAP kinases and NF-kappaB.
- SAA's dual action on TF and TFPI highlights its complex role in vascular hemostasis and CAD pathogenesis.
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 microg/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 microg/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 NFkappaB inhibitor (Bay-11 to 7082) could block SAA-dependent TF induction. SAA also directly induced activation of MAP kinases and NFkappaB.
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 NFkappaB.
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