Serum amyloid A stimulates lipoprotein-associated phospholipase A2 expression in vitro and in vivo

Objectives: Although lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) has been regarded as a biomarker and a causative agent for acute coronary events recently, the mechanism of the regulation of Lp-PLA(2) has not been fully elucidated yet. This study was aimed to investigate the influence of serum amyloid A (SAA) on the expression of Lp-PLA(2) in THP-1 cells and ApoE-deficient (ApoE(-/-)) mice. Methods: THP-1 cells were stimulated by SAA and the mRNA and protein expression of Lp-PLA(2) was detected. ApoE(-/-) mice were intravenously injected with murine SAA1 lentivirus. Formyl peptide receptor like-1 (FPRL1) agonist (WKYMVm) and inhibitor (WRW4), mitogen-activated protein kinases (MAPKs) inhibitors, and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist and inhibitor were used to investigate the mechanism of regulation of Lp-PLA(2). Results: Recombinant SAA up-regulated Lp-PLA(2) expression in a dose and time-dependent manner in THP-1 cells. Immunohistochemical analysis of aortic root of ApoE(-/-) mice also demonstrated that the expression of Lp-PLA(2) was up-regulated significantly with SAA treatment. WRW4 decreased SAA-induced Lp-PLA(2) production; while WKYMVm could induce Lp-PLA(2) expression. ERK1/2, JNK1/2, and p38 inhibition reduced SAA-induced Lp-PLA(2) production. Furthermore, the results suggested the activation of PPAR-gamma played a crucial role in this process. Conclusion: These results demonstrate that SAA up-regulates Lp-PLA(2) production significantly via a FPRL1/MAPKs./PPAR-gamma signaling pathway. (C) 2013 Elsevier Ireland Ltd. All rights reserved.