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

Abstract 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 (WRW 4 ), mitogen-activated protein kinases (MAPKs) inhibitors, and peroxisome proliferator-activated receptor-γ (PPAR-γ) 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. WRW 4 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-γ 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-γ signaling pathway.