PEDF improves atherosclerotic plaque stability by inhibiting macrophage inflammation response

Background: Atherosclerosis is a vascular disease with plaque formation and growth. Instable plaque with chronic inflammation is closely related to adverse cardiac outcomes. Pigment epithelium-derived factor (PEDF) is an endogenous multifunctional cytokine that possesses the ability of anti-inflammation. The aim of this study is to detect whether PEDF has protective effect on the stability of atherosclerotic plaque and to explore whether the effect of anti-inflammation involved. Methods and results: ApoE(-/-) mice fed with high fat diet and RAW264.7 cells were used to evaluate anti-inflammatory activities of PEDF both in vivo and in vitro. PEDF overexpression improved atherosclerotic plaque stability in ApoE(-/-) mice. The expression of inflammatory factors (interleukin-1 beta [IL-1 beta], interleukin-6 [IL-6], tumor necrosis factor-alpha [TNF-alpha], monocyte chemotactic protein-1 [MCP-1] and matrix metalloproteinase [MMP-9]) was significantly decreasedwith PEDF overexpression in vivo and in vitro. The anti-inflammation effect of PEDF was attenuated by PPAR-gamma specific antagonist GW9662. In addition, PEDF significantly decreased the expression of phosphorylated ERK-MAPK, p38-MAPK and JNK-MAPK. GW9662 partly reversed the PEDF-mediated depression of phosphorylated ERK- and p38-MAPK but has no significant effect on JNK-MAPK. Conclusions: PEDF has protective effect on increasing AS plaque stability through ameliorating macrophage inflammation. PPAR-gamma and downstream MAPKs were involved in the mechanism. (C) 2017 Published by Elsevier B.V.