title: Coenzyme Q10 promotes macrophage cholesterol efflux by regulation of the activator protein-1/miR-378/ATP-binding cassette transporter G1-signaling pathway.
abstract: OBJECTIVE
  Recent studies have shown the role of miRNAs in macrophage reverse cholesterol transport and atherogenesis. We hypothesized that coenzyme Q10 (CoQ10) may increase macrophage reverse cholesterol transport by regulating miRNA expression that contributes to the prevention of atherosclerosis.
  
  
  RESULTS
  CoQ10 treatment suppressed oxidized low-density lipoprotein-induced macrophage foam cell formation by ameliorating the binding of activator protein-1 to the putative promoter region of miR-378 primary transcript, thus decreasing the miR-378 level and enhancing the ATP-binding cassette transporter G1-mediated macrophage cholesterol efflux to high-density lipoprotein. Subsequently, the axis of activator protein-1/miR-378/ATP-binding cassette transporter G1 cholesterol efflux was confirmed in peritoneal macrophages isolated from CoQ10-treated apolipoprotein E-deficient mice. Finally, CoQ10 consumption promoted macrophage reverse cholesterol transport and inhibited the progression of atherosclerosis in apolipoprotein E-deficient mice.
  
  
  CONCLUSIONS
  This study identified activator protein-1/miR-378/ATP-binding cassette transporter G1 as a novel cascade for CoQ10 in facilitating macrophage cholesterol efflux in vitro and in vivo. Our data thus imply that both CoQ10 and miR-378 are promising candidates for atherosclerosis prevention and treatment.
authors.affiliation: From the Department of Nutrition, School of Public Health, Sun Yat-Sen University (Northern Campus), Guangzhou, Guangdong Province, People's Republic of China (D.W., X.Y., M.X., Y.Y., D.L., X.L., F.S., W.L.); and Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University (Northern Campus), Guangzhou, Guangdong Province, People's Republic of China (D.W., M.X., Y.Y., D.L., W.L.).
authors.forename: Dongliang
authors.initials: D
authors.lastname: Wang
authors.affiliation: From the Department of Nutrition, School of Public Health, Sun Yat-Sen University (Northern Campus), Guangzhou, Guangdong Province, People's Republic of China (D.W., X.Y., M.X., Y.Y., D.L., X.L., F.S., W.L.); and Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University (Northern Campus), Guangzhou, Guangdong Province, People's Republic of China (D.W., M.X., Y.Y., D.L., W.L.).
authors.forename: Xiao
authors.initials: X
authors.lastname: Yan
authors.affiliation: From the Department of Nutrition, School of Public Health, Sun Yat-Sen University (Northern Campus), Guangzhou, Guangdong Province, People's Republic of China (D.W., X.Y., M.X., Y.Y., D.L., X.L., F.S., W.L.); and Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University (Northern Campus), Guangzhou, Guangdong Province, People's Republic of China (D.W., M.X., Y.Y., D.L., W.L.).
authors.forename: Min
authors.initials: M
authors.lastname: Xia
authors.affiliation: From the Department of Nutrition, School of Public Health, Sun Yat-Sen University (Northern Campus), Guangzhou, Guangdong Province, People's Republic of China (D.W., X.Y., M.X., Y.Y., D.L., X.L., F.S., W.L.); and Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University (Northern Campus), Guangzhou, Guangdong Province, People's Republic of China (D.W., M.X., Y.Y., D.L., W.L.).
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: From the Department of Nutrition, School of Public Health, Sun Yat-Sen University (Northern Campus), Guangzhou, Guangdong Province, People's Republic of China (D.W., X.Y., M.X., Y.Y., D.L., X.L., F.S., W.L.); and Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University (Northern Campus), Guangzhou, Guangdong Province, People's Republic of China (D.W., M.X., Y.Y., D.L., W.L.).
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: From the Department of Nutrition, School of Public Health, Sun Yat-Sen University (Northern Campus), Guangzhou, Guangdong Province, People's Republic of China (D.W., X.Y., M.X., Y.Y., D.L., X.L., F.S., W.L.); and Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University (Northern Campus), Guangzhou, Guangdong Province, People's Republic of China (D.W., M.X., Y.Y., D.L., W.L.).
authors.forename: Xinrui
authors.initials: X
authors.lastname: Li
authors.affiliation: From the Department of Nutrition, School of Public Health, Sun Yat-Sen University (Northern Campus), Guangzhou, Guangdong Province, People's Republic of China (D.W., X.Y., M.X., Y.Y., D.L., X.L., F.S., W.L.); and Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University (Northern Campus), Guangzhou, Guangdong Province, People's Republic of China (D.W., M.X., Y.Y., D.L., W.L.).
authors.forename: Fenglin
authors.initials: F
authors.lastname: Song
authors.affiliation: From the Department of Nutrition, School of Public Health, Sun Yat-Sen University (Northern Campus), Guangzhou, Guangdong Province, People's Republic of China (D.W., X.Y., M.X., Y.Y., D.L., X.L., F.S., W.L.); and Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University (Northern Campus), Guangzhou, Guangdong Province, People's Republic of China (D.W., M.X., Y.Y., D.L., W.L.). lingwh@mail.sysu.edu.cn.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Ling
mesh_terms: D020413:3' Untranslated Regions; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000378:metabolism*; D005487:Foam Cells / Q000187:drug effects / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008074:Lipoproteins / Q000235:genetics / Q000502:physiology*; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000502:physiology*; D014162:Transfection; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology
chemical_list: D020413:3' Untranslated Regions; C419353:ABCG1 protein, human; C487540:ABCG1 protein, mouse; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D001057:Apolipoproteins E; D008074:Lipoproteins; D008077:Lipoproteins, LDL; C526012:MIRN378 microRNA, human; C546119:MIRN378 microRNA, mouse; D035683:MicroRNAs; D034741:RNA, Small Interfering; D018808:Transcription Factor AP-1; C099252:oxidized low density lipoprotein; D014451:Ubiquinone; D002784:Cholesterol; C024989:coenzyme Q10
keywords: atherosclerosis; coenzyme Q10; macrophages; miRNAs