Perivascular adipose tissue-derived adiponectin inhibits collar-induced carotid atherosclerosis by promoting macrophage autophagy.

Perivascular adipose tissue-derived adiponectin inhibits collar-induced carotid atherosclerosis by promoting macrophage autophagy.
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血管周围脂肪组织来源的脂联素通过促进巨噬细胞自噬抑制项圈诱导的颈动脉粥样硬化。

DOI:
10.1371/journal.pone.0124031
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Zhao Y
Zhao Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Li C;Wang Z;Wang C;Ma Q;Zhao Y

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血管周围脂肪组织(PVAT)分泌的脂联素(APN)是抑制动脉粥样硬化发展的重要抗炎脂肪因子之一,但其机制尚不清楚。在这项研究中,我们的目的是阐明APN如何调节动脉粥样硬化斑块的形成。为了评估PVAT分泌的APN在动脉粥样硬化进展中的作用,我们在颈动脉粥样硬化模型上进行了PVAT移植实验:ApoE敲除(ApoE−/−)小鼠,左颈动脉周围血管周围放置项圈,并结合高脂饮食喂养。我们的结果表明,与移植野生型同窝组织的Apoe-/-小鼠相比,来自APN敲除(APN-/-)小鼠的患有PVAT的Apoe-/-小鼠表现出更快的斑块体积形成。相反,与对照组相比,ApoE−/−小鼠移植APN-/-小鼠衍生的PVAT后,巨噬细胞中的自噬显著减弱。此外,体外研究表明APN处理增加了原代巨噬细胞中的自噬,如通过增加的LC 3-I加工和Beclin 1表达所证明的,其伴随着p62的下调。此外,我们的研究结果表明,APN通过抑制Akt/FOXO 3a信号通路促进巨噬细胞自噬。我们的研究结果表明,PVAT分泌APN抑制斑块形成诱导巨噬细胞自噬。
Adiponectin (APN) secreted from perivascular adipose tissue (PVAT) is one of the important anti-inflammatory adipokines to inhibit the development of atherosclerosis, but the underlying mechanism has not been clarified. In this study, we aimed to elucidate how APN regulates plaque formation in atherosclerosis. To assess the role of APN secreted by PVAT in atherosclerosis progression, we performed PVAT transplantation experiments on carotid artery atherosclerosis model: ApoE knockout (ApoE−/−) mice with a perivascular collar placement around the left carotid artery in combination with a high-fat diet feeding. Our results show that the ApoE−/− mice with PVAT derived from APN knockout (APN−/−) mice exhibited accelerated plaque volume formation compared to ApoE−/− mice transplanted with wild-type littermate tissue. Conversely, autophagy in macrophages was significantly attenuated in ApoE−/− mice transplanted with APN-/- mouse-derived PVAT compared to controls. Furthermore, in vitro studies indicate that APN treatment increased autophagy in primary macrophages, as evidenced by increased LC3-I processing and Beclin1 expression, which was accompanied by down-regulation of p62. Moreover, our results demonstrate that APN promotes macrophage autophagy via suppressing the Akt/FOXO3a signaling pathway. Our results indicate that PVAT-secreted APN suppresses plaque formation by inducing macrophage autophagy.
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