title: Simvastatin enhances oxidized‑low density lipoprotein‑induced macrophage autophagy and attenuates lipid aggregation.
abstract: Macrophage autophagy exerts a protective effect in advanced atherosclerosis. It has previously been reported that oxidized low‑density lipoprotein (ox‑LDL) induces autophagy in endothelial cells, and simvastatin enhances autophagy in coronary arterial myocytes. However, it is currently unknown whether ox‑LDL induces autophagy in macrophages, or whether simvastatin affects macrophage autophagy in atherosclerosis. The present study demonstrated that ox‑LDL induced lipid accumulation in the J774A.1 macrophage cell line, in a dose‑dependent manner, as determined by oil red O staining. Ox‑LDL also induced autophagy in the J774A.1 cells, by converting microtubule‑associated protein 1 light chain 3 (LC3) I to LC3 II, which is a well‑known autophagy marker. Notably, treatment of the cells with simvastatin elevated ox‑LDL‑induced macrophage autophagy, this was detected through the conversion of LC3 I to LC3 II and the increased expression of Beclin1, another autophagy marker. Furthermore, it was shown that stimulation with ox‑LDL led to the redistribution of green fluorescent protein (GFP)‑LC3 from diffusion distribution, to the formation of puncta in the J774A.1 cells. Simvastatin promoted the ox‑LDL‑induced formation of GFP‑LC3 puncta, as detected by confocal laser scanning microscopy. Simvastatin was also shown to inhibit ox‑LDL‑induced cholesterol accumulation in the J774A.1 cells, as observed by oil red O staining and CHOD‑PAP assay. These results suggest that simvastatin may enhance ox‑LDL‑induced macrophage autophagy and attenuate lipid aggregation.
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Baojun
authors.initials: B
authors.lastname: Huang
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Mengxing
authors.initials: M
authors.lastname: Jin
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Hai
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Comprehensive Laboratory, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Dake
authors.initials: D
authors.lastname: Huang
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Songcheng
authors.initials: S
authors.lastname: Ying
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Linjie
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000633:toxicity; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D019821:Simvastatin / Q000494:pharmacology*
chemical_list: D000924:Anticholesteremic Agents; D008077:Lipoproteins, LDL; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; C099252:oxidized low density lipoprotein; D002784:Cholesterol; D019821:Simvastatin