Research Paper Volume 11, Issue 23 pp 10992—11009

Mangiferin promotes macrophage cholesterol efflux and protects against atherosclerosis by augmenting the expression of ABCA1 and ABCG1

Kun Ren 1, 2, *, , Heng Li 3, *, , Hui-Fang Zhou 3, *, , Yin Liang 3, , Min Tong 2, , Lu Chen 2, , Xi-Long Zheng 4, 5, , Guo-Jun Zhao 1, 6, ,

  • 1 The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan City People’s Hospital, Qingyuan, Guangdong, China
  • 2 Department of Pathophysiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, China
  • 3 Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, University of South China, Hengyang, Hunan, China
  • 4 Department of Biochemistry and Molecular Biology, The Libin Cardiovascular Institute of Alberta, The University of Calgary, Health Sciences Center, Calgary, AB, Canada
  • 5 Key Laboratory of Molecular Targets and Clinical Pharmacology, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China
  • 6 Department of Histology and Embryology, Guilin Medical University, Guilin, Guangxi, China
* Equal contribution

received: July 31, 2019 ; accepted: November 17, 2019 ; published: December 2, 2019 ;

https://doi.org/10.18632/aging.102498
How to Cite

Copyright © 2019 Ren et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Mangiferin has been identified as a potent cardioprotective factor that enhances high-density lipoprotein cholesterol levels in plasma. The aim of this study was to investigate the impact of mangiferin on macrophage cholesterol efflux and the development of atherosclerosis. The results showed that mangiferin injection significantly decreased atherosclerotic plaque size, and reduced plasma levels of low-density lipoprotein cholesterol, triglyceride, and total cholesterol in apoE knockout mice, whereas reverse cholesterol transport efficiency and high-density lipoprotein cholesterol levels were enhanced. In vitro study showed that mangiferin prevented lipid accumulation and promoted [3H]-cholesterol efflux from acetylated LDL-loaded RAW264.7 macrophages with an increase in the expression of ATP binding cassette A1/G1 (ABCA1/G1), liver X receptor-α (LXRα) and peroxisome proliferator-activated receptor-γ (PPARγ). Moreover, transfection of PPARγ siRNA or LXRα siRNA markedly abolished the positive effects of mangiferin on ABCA1/G1 expression and cholesterol efflux. The opposite effects were observed after treatment with PPARγ agonist rosiglitazone or LXRα agonist T0901317. In conclusion, mangiferin may attenuate atherogenesis by promoting cholesterol efflux from macrophages via the PPARγ-LXRα-ABCA1/G1 pathway.

Abbreviations

CVD: cardiovascular disease; AS: atherosclerosis; HDL: High-density lipoprotein; RCT: reverse cholesterol transport; ABCA1/G1: ATP-binding cassette transporter A1/G1; HDL-C: HDL cholesterol; PPARγ: peroxisome proliferators-activated receptor-γ; LXRα: liver X receptor-α; RXR: retinoid X receptor; TG: triglyceride; TC: total cholesterol; LDL-C: low-density lipoprotein cholesterol; FFA: free fatty acid; LPL: lipoprotein lipase; VLDL-C: very low-density lipoprotein cholesterol; GLUT4: glucose transporter type 4; HFD: high-fat diet; IL-1β: interleukin-1β; MMP-1: matrix metalloproteinase-1; LSC: liquid scintillation counting; HPLC: high-performance liquid chromatography; FC: free cholesterol; CE: cholesteryl ester; DMY: dihydromyricetin; Hcy: homocysteine; 9-cis-RA: 9-cis-retinoic acid; PPRE: PPAR response element; PPARγ-/- BMT: PPARγ-/- bone marrow; CUMS: chronic unpredictable mild stress; CGA: chlorogenic acid; PBS: phosphate-buffered saline; O.C.T.: optimal cutting temperature; FBS: fetal bovine serum; ac-LDL: acetylated-low density lipoprotein; BSA: bovine serum albumin; MTT: 3-(4: 5-dimethylthiazol-2-yl)-2: 5-diphenyltetrazolium bromide; RIPA: radioimmunoprecipitation assay; PMSF: phenylmethylsulfonyl fluoride; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis; PVDF: polyvinylidene fluoride membranes; TBS-T: Tween-20 Tris-buffered saline; ECL: enhanced chemiluminescence; SEM: standard error of the mean; SNK: Student-Newman-Keuls.