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

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

  • Biochim Biophys Acta Mol Cell Biol Lipids. 2024 Jul 14;1869(7):159533. doi: 10.1016/j.bbalip.2024.159533.
Qinyi Zhou 1 Yang Wang 2 Yaqiong Cheng 2 Jing Zhou 2 Wang Liu 3 Xiaofeng Ma 4 Shilin Tang 5 Shangshu Tang 6 Chaoke Tang 7
Affiliations

Affiliations

  • 1 Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China; Department of Cardiology, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
  • 2 Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
  • 3 Department of Gastrointestinal Surgery, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China.
  • 4 Department of Cardiology, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
  • 5 Department of Critical Care Medicine, the First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
  • 6 The Seventh Affiliated Hospital University of South China / Hunan Veterans Administration Hospital, Hengyang Medical School, University of South China, Changsha, Hunan, China. Electronic address: 593572529@qq.com.
  • 7 Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China. Electronic address: 1981001337@usc.edu.cn.
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.

Keywords

ABCA1; Atherosclerosis; Cholesterol efflux; Ilexgenin A; PTPN2.

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