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Atherosclerosis. 2009 Feb;202(2):596-604. doi: 10.1016/j.atherosclerosis.2008.04.049. Epub 2008 May 15.

Serum amyloid A may potentiate prothrombotic and proinflammatory events in acute coronary syndromes.

Author information

1
Department of Cardiology, Concord Repatriation General Hospital and Vascular Biology Laboratory, ANZAC Research Institute, University of Sydney, Sydney, Australia.

Abstract

AIMS:

Elevated serum amyloid A (SAA) levels, like C-reactive protein (CRP), predict coronary events. Both induce monocyte tissue factor (TF), and peripheral blood mononuclear cells (PBMC) from patients with coronary artery disease (CAD) express higher TF in response to CRP. This study examined SAA induction of TF and tumour necrosis factor-alpha (TNF) in PBMC from patients with CAD and in monocytoid THP-1 cells.

METHODS AND RESULTS:

PBMC from 26 males with CAD (15 stable angina, SA, and 11 acute coronary syndromes, ACS) and 14 male controls were stimulated with SAA. SAA promoted up to six-fold increase in TF activity (recalcification assay) on PBMC from patients, associated with elevated TF mRNA and protein. PBMC responded optimally when monocytes were adherent. Unlike CRP, SAA induced TF and TNF in THP-1 cells. SAA-induced TNF was dose-dependently inhibited by HDL. PBMC from patients with ACS expressed more basal TF (257.4+/-46.8 mU/10(6) PBMC vs. 131.0+/-12.5 mU/10(6) PBMC, P=0.003), and greater SAA-induced TF than cells from controls, whereas no difference was found between SA and controls (ACS 2246+/-493, SA 1364+/-206, controls 1091+/-113 mU/10(6) PBMC, with SAA 250 ng/mL, P=0.002 ACS vs. controls across the dose range). Importantly, SAA-induced TNF levels (ELISA) were much higher in patients with ACS than SA or controls (ACS 211+/-41, SA 108+/-16, controls 73+/-11 pg/mL, with SAA 250 ng/mL, P=0.001 ACS vs. controls or P=0.013 ACS vs. SA across the dose range). SAA-induced TF and TNF correlated positively with serum SAA levels in CAD, but not controls.

CONCLUSIONS:

SAA is a prothrombotic and proinflammatory mediator in ACS which may contribute to atherogenesis and its complications.

[Indexed for MEDLINE]

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