Impact of serum amyloid A on tissue factor and tissue factor pathway inhibitor expression and activity in endothelial cells.
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.


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.
Zhao
Yulan
Y
Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, 5, Lower Kent Ridge Rd, Singapore 119074.
Zhou
Shuli
S
Heng
Chew-Kiat
CK
D015153:Blotting, Western; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000503:physiopathology; D003331:Coronary Vessels / Q000166:cytology; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism / Q000494:pharmacology*; D011336:Probability; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D000685:Serum Amyloid A Protein / Q000494:pharmacology*; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology
D008074:Lipoproteins; D000685:Serum Amyloid A Protein; C051928:lipoprotein-associated coagulation inhibitor; D013925:Thromboplastin