Ilexgenin A inhibits lipid accumulation in macrophages and reduces the progression of atherosclerosis through PTPN2/ERK1/2/ABCA1 signalling pathway

IF 3.9 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular and cell biology of lipids Pub Date : 2024-07-14 DOI:10.1016/j.bbalip.2024.159533

Qinyi Zhou , Yang Wang , Yaqiong Cheng , Jing Zhou , Wang Liu , Xiaofeng Ma , Shilin Tang , Shangshu Tang , Chaoke Tang

{"title":"Ilexgenin A inhibits lipid accumulation in macrophages and reduces the progression of atherosclerosis through PTPN2/ERK1/2/ABCA1 signalling pathway","authors":"Qinyi Zhou , Yang Wang , Yaqiong Cheng , Jing Zhou , Wang Liu , Xiaofeng Ma , Shilin Tang , Shangshu Tang , Chaoke Tang","doi":"10.1016/j.bbalip.2024.159533","DOIUrl":null,"url":null,"abstract":"<div><p>Macrophage lipid accumulation indicates a pathological change in atherosclerosis. Ilexgenin A (IA), a pentacyclic triterpenoid compound, plays a role in preventing inflammation, bacterial infection, and fatty liver and induces a potential anti-atherogenic effect. However, the anti-atherosclerotic mechanism remains unclear. The present study investigated the effects of IA on lipid accumulation in macrophage-derived foam cells and atherogenesis in apoE<sup>−/−</sup> mice. Our results indicated that the expression of adenosine triphosphate-binding cassette transporter A1 (ABCA1) was up-regulated by IA, promoting cholesterol efflux and reducing lipid accumulation in macrophages, which may be regulated by the protein tyrosine phosphatase non-receptor type 2 (PTPN2)/ERK1/2 signalling pathway. IA attenuated the progression of atherosclerosis in high-fat diet-fed apoE<sup>−/−</sup> mice. PTPN2 knockdown with siRNA or treatment with an ERK1/2 agonist (Ro 67–7476) impeded the effects of IA on ABCA1 upregulation and cholesterol efflux in macrophages. These results suggest that IA inhibits macrophage lipid accumulation and alleviates atherosclerosis progression via the PTPN2/ERK1/2 signalling pathway.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 7","pages":"Article 159533"},"PeriodicalIF":3.9000,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochimica et biophysica acta. Molecular and cell biology of lipids","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1388198124000830","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Macrophage lipid accumulation indicates a pathological change in atherosclerosis. Ilexgenin A (IA), a pentacyclic triterpenoid compound, plays a role in preventing inflammation, bacterial infection, and fatty liver and induces a potential anti-atherogenic effect. However, the anti-atherosclerotic mechanism remains unclear. The present study investigated the effects of IA on lipid accumulation in macrophage-derived foam cells and atherogenesis in apoE^−/− mice. Our results indicated that the expression of adenosine triphosphate-binding cassette transporter A1 (ABCA1) was up-regulated by IA, promoting cholesterol efflux and reducing lipid accumulation in macrophages, which may be regulated by the protein tyrosine phosphatase non-receptor type 2 (PTPN2)/ERK1/2 signalling pathway. IA attenuated the progression of atherosclerosis in high-fat diet-fed apoE^−/− mice. PTPN2 knockdown with siRNA or treatment with an ERK1/2 agonist (Ro 67–7476) impeded the effects of IA on ABCA1 upregulation and cholesterol efflux in macrophages. These results suggest that IA inhibits macrophage lipid accumulation and alleviates atherosclerosis progression via the PTPN2/ERK1/2 signalling pathway.

查看原文本刊更多论文

Ilexgenin A 可通过 PTPN2/ERK1/2/ABCA1 信号通路抑制巨噬细胞中的脂质积聚并减少动脉粥样硬化的进展。

巨噬细胞脂质积累是动脉粥样硬化的一种病理变化。Ilexgenin A（IA）是一种五环三萜类化合物，在预防炎症、细菌感染和脂肪肝方面发挥作用，并具有潜在的抗动脉粥样硬化作用。然而，其抗动脉粥样硬化的机制仍不清楚。本研究探讨了 IA 对巨噬细胞衍生的泡沫细胞中脂质积累和载脂蛋白 E-/- 小鼠动脉粥样硬化发生的影响。结果表明，IA上调三磷酸腺苷结合盒转运体A1（ABCA1）的表达，促进胆固醇外流，减少巨噬细胞中的脂质积累，这可能是受蛋白酪氨酸磷酸酶非受体2型（PTPN2）/ERK1/2信号通路的调控。IA 可减轻高脂饮食喂养的载脂蛋白E-/-小鼠动脉粥样硬化的进展。用 siRNA 敲除 PTPN2 或用 ERK1/2 激动剂（Ro 67-7476）抑制 IA 对巨噬细胞中 ABCA1 上调和胆固醇外流的影响。这些结果表明，IA 可通过 PTPN2/ERK1/2 信号通路抑制巨噬细胞的脂质积累并缓解动脉粥样硬化的进展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Biochimica et biophysica acta. Molecular and cell biology of lipids 生物-生化与分子生物学

CiteScore

11.00

自引率

2.10%

发文量

109

审稿时长

53 days

期刊介绍： BBA Molecular and Cell Biology of Lipids publishes papers on original research dealing with novel aspects of molecular genetics related to the lipidome, the biosynthesis of lipids, the role of lipids in cells and whole organisms, the regulation of lipid metabolism and function, and lipidomics in all organisms. Manuscripts should significantly advance the understanding of the molecular mechanisms underlying biological processes in which lipids are involved. Papers detailing novel methodology must report significant biochemical, molecular, or functional insight in the area of lipids.