PEDF improves atherosclerotic plaque stability by inhibiting macrophage inflammation response
PEDF improves atherosclerotic plaque stability by inhibiting macrophage inflammation response
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PEDF 通过抑制巨噬细胞炎症反应改善动脉粥样硬化斑块稳定性
DOI：
10.1016/j.ijcard.2017.02.102
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发表时间：
2017-05-15
影响因子：
3.5
通讯作者：
Lu, Huixia
中科院分区：
文献类型：
--
作者：
Wen, Hao;Liu, Minghao;Lu, Huixia
背景：动脉粥样硬化是一种以斑块形成和生长为特征的血管疾病。不稳定斑块伴慢性炎症与不良心脏结局密切相关。色素上皮衍生因子（PEDF）是一种内源性多功能细胞因子，具有抗炎作用。本研究旨在探讨PEDF对动脉粥样硬化斑块的稳定性是否具有保护作用，并探讨其抗炎作用是否参与其中。方法和结果：采用高脂饲料喂养的ApoE（-/-）小鼠和RAW264.7细胞，评价PEDF的体内外抗炎活性。PEDF过表达改善ApoE（-/-）小鼠动脉粥样硬化斑块的稳定性。在体内和体外，PEDF过表达可显著降低炎症因子（白细胞介素-1 β [IL-1 β]、白细胞介素-6 [IL-6]、肿瘤坏死因子-α [TNF-α]、单核细胞趋化蛋白-1 [MCP-1]和基质金属蛋白酶[MMP-9]）的表达。PPAR-gamma特异性拮抗剂GW 9662可减弱PEDF的抗炎作用。此外，PEDF还能显著降低磷酸化ERK-MAPK、p38-MAPK和JNK-MAPK的表达。GW 9662可部分逆转PEDF对ERK-和p38-MAPK磷酸化的抑制作用，但对JNK-MAPK无明显影响。结论：PEDF通过减轻巨噬细胞炎症反应，对AS斑块稳定性有保护作用。PPAR-gamma和下游MAPK参与了这一机制。(C)2017由Elsevier B. V.出版
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.