title: Retinoic acid induces macrophage cholesterol efflux and inhibits atherosclerotic plaque formation in apoE-deficient mice.
abstract: It has been suggested that retinoic acid (RA) has a potential role in the prevention of atherosclerotic CVD. In the present study, we used J774A.1 cell lines and primary peritoneal macrophages to investigate the protective effects of RA on foam cell formation and atherogenesis in apoE-deficient (apoE- / -) mice. A total of twenty male apoE- / - mice (n 10 animals per group), aged 8 weeks, were fed on a high-fat diet (HFD) and treated with vehicle or 9-cis-RA for 8 weeks. The atherosclerotic plaque area in the aortic sinus of mice in the 9-cis-RA group was 40·7 % less than that of mice in the control group (P< 0·01). Mouse peritoneal macrophages from the 9-cis-RA group had higher protein expression levels of ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1) than those from the control group. Serum total and LDL-cholesterol concentrations were lower in the 9-cis-RA group than in the control group (P< 0·05). In vitro studies showed that incubation of cholesterol-loaded J774A.1 macrophages with 9-cis-RA (0·1, 1 and 10 μmol/l) induced cholesterol efflux in a dose-dependent manner. The 9-cis-RA treatment markedly attenuated lipid accumulation in macrophages exposed to oxidised LDL. Moreover, treatment with 9-cis-RA significantly increased the protein expression levels of ABCA1 and ABCG1 in J774A.1 macrophages in a dose-dependent manner. Furthermore, 9-cis-RA dose-dependently enhanced the protein expression level of liver X receptor-α (LXRα), the upstream regulator of ABCA1 and ABCG1. Taken together, the present results show that 9-cis-RA suppresses foam cell formation and prevents HFD-induced atherogenesis via the LXRα-dependent up-regulation of ABCA1 and ABCG1.
authors.affiliation: Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University (Northern Campus),Guangzhou,Guangdong Province510080,People's Republic of China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University,Guangzhou,Guangdong Province510055,People's Republic of China.
authors.forename: Jiacheng
authors.initials: J
authors.lastname: Lin
authors.affiliation: Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University (Northern Campus),Guangzhou,Guangdong Province510080,People's Republic of China.
authors.forename: Hongen
authors.initials: H
authors.lastname: Chen
authors.affiliation: Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University (Northern Campus),Guangzhou,Guangdong Province510080,People's Republic of China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University (Northern Campus),Guangzhou,Guangdong Province510080,People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University (Northern Campus),Guangzhou,Guangdong Province510080,People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Xia
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism*; D000077556:Alitretinoin; D000818:Animals; D001011:Aorta; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000097:blood; D059305:Diet, High-Fat; D005487:Foam Cells / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D000071518:Liver X Receptors; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018345:Mice, Knockout; D057093:Orphan Nuclear Receptors / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000378:metabolism / Q000517:prevention & control*; D014212:Tretinoin / Q000494:pharmacology / Q000627:therapeutic use*; D015854:Up-Regulation
chemical_list: D064286:ATP Binding Cassette Transporter 1; D001057:Apolipoproteins E; D008078:Cholesterol, LDL; D008077:Lipoproteins, LDL; D000071518:Liver X Receptors; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; C099252:oxidized low density lipoprotein; D000077556:Alitretinoin; D014212:Tretinoin; D002784:Cholesterol
keywords: ApoE-deficient mice; Atherosclerosis; Macrophage cholesterol efflux; Retinoic acid