Yulan Zhao1, Shuli Zhou, Chew-Kiat Heng. 1. Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, 5, Lower Kent Ridge Rd, Singapore 119074.
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 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.
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.
Authors: Wanessa Araújo Carvalho; Sandra Regina Maruyama; Alessandra Mara Franzin; Antônio Roberto Rodrigues Abatepaulo; Jennifer M Anderson; Beatriz Rossetti Ferreira; José Marcos Chaves Ribeiro; Daniela Dantas Moré; Antonio Augusto Mendes Maia; Jesus G Valenzuela; Gustavo Rocha Garcia; Isabel K Ferreira de Miranda Santos Journal: Exp Parasitol Date: 2010-01-04 Impact factor: 2.011