%0 Journal Article
%T Ilexgenin A inhibits lipid accumulation in macrophages and reduces the progression of atherosclerosis through PTPN2/ERK1/2/ABCA1 signalling pathway.
%A Zhou Q
%A Wang Y
%A Cheng Y
%A Zhou J
%A Liu W
%A Ma X
%A Tang S
%A Tang S
%A Tang C
%J Biochim Biophys Acta Mol Cell Biol Lipids
%V 1869
%N 7
%D 2024 Oct 14
%M 39009241
%F 5.228
%R 10.1016/j.bbalip.2024.159533
%X 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.