title: Curcumin retunes cholesterol transport homeostasis and inflammation response in M1 macrophage to prevent atherosclerosis.
abstract: Lipoprotein cholesterol metabolism dysfunction in the arterial wall is a major contributor to atherosclerosis, and excessive lipid intake and failed cholesterol homeostasis may accelerate the atherogenic process. Curcumin exerts multiple effects by alleviating inflammation, hyperlipidemia, and atherosclerosis; however, its role in cholesterol transport homeostasis and its underlying impact on inflammatory M1 macrophages are poorly understood. This work aimed to investigate the effect of curcumin on cholesterol transport, the inflammatory response and cell apoptosis in M1 macrophages. RAW264.7 macrophages (M0) were induced with LPS plus IFN-γ for 12 h to develop a M1 subtype and were then incubated with curcumin at different concentrations (6.25 and 12.5 μmol/L) in the presence or absence of oxLDL. Then, cholesterol influx/efflux and foam cell formation as well as inflammation and apoptosis were evaluated. It was found that curcumin increased cholesterol uptake measured by the Dil-oxLDL binding assay, and simultaneously increased cholesterol efflux carried out by Apo-A1 and HDL in M1 cells. Curcumin further reinforced ox-LDL-induced cholesterol esterification and foam cell formation as determined by Oil Red O and BODIPY staining. Moreover, curcumin dramatically reduced ox-LDL-induced cytokine production such as IL-1β, IL-6 as well as TNF-α and M1 cell apoptosis. We also found that curcumin upregulated CD36 and ABCA1 in M1 macrophages. Curcumin increased PPARγ expression, which in turn promoted CD36 and ABCA1 expression. In conclusion, curcumin may increase the ability of M1 macrophages to handle harmful lipids, thus promoting lipid processing, disposal and removal, which may support cholesterol homeostasis and exert an anti-atherosclerotic effect.
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Fang-Yuan
authors.initials: FY
authors.lastname: Chen
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. Electronic address: guoning_gn@163.com.
authors.forename: Ning
authors.initials: N
authors.lastname: Guo
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Wang-Ge
authors.initials: WG
authors.lastname: Ma
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Zu-Yi
authors.initials: ZY
authors.lastname: Yuan
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism; D000818:Animals; D050197:Atherosclerosis / Q000517:prevention & control*; D001692:Biological Transport; D018955:CD36 Antigens / Q000378:metabolism; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D003474:Curcumin / Q000494:pharmacology*; D004951:Esterification; D006706:Homeostasis / Q000187:drug effects*; D007249:Inflammation / Q000517:prevention & control*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism
chemical_list: D064286:ATP Binding Cassette Transporter 1; D018955:CD36 Antigens; D002784:Cholesterol; D003474:Curcumin; D047495:PPAR gamma; C577833:Abca1 protein, mouse
keywords: Cholesterol efflux; Cholesterol uptake; Curcumin; Inflammation; M1 macrophages; PPARγ