title: Increased atherosclerotic lesions in LDL receptor deficient mice with hematopoietic nuclear receptor Rev-erbα knock- down.
abstract: BACKGROUND
  Nuclear receptor Rev-erbα plays important roles in circadian clock timing, lipid metabolism, adipogenesis, and vascular inflammation. However, the role of Rev-erbα in atherosclerotic lesion development has not been assessed in vivo.
  
  
  RESULTS
  The nuclear receptor Rev-erbα was knocked down in mouse haematopoietic cells by means of shRNA-lentiviral transduction, followed by bone marrow transplantation into LDL receptor knockout mice. The Rev-erbα protein in peripheral macrophage was reduced by 70% as compared to control mice injected with nontargeting shRNA lentivirus-transduced bone marrow. A significant increase in atherosclerotic lesions was observed around the aorta valves as well as upon en face aorta analysis of Rev-erbα knock-down bone marrow recipients (P<0.01) as compared to the control mice, while plasma cholesterol, phospholipid, and triacylglycerol levels were not affected. Overexpression of Rev-erbα in bone marrow mononuclear cells decreased inflammatory M1 while increasing M2 macrophage markers, while Rev-erbα knock down increased the macrophage inflammatory phenotype in vitro and in vivo. Furthermore, treatment of differentiating macrophages with the Rev-erbα ligand heme promoted expression of antiinflammatory M2 markers.
  
  
  CONCLUSIONS
  These observations identify hematopoietic cell Rev-erbα as a new modulator of atherogenesis in mice.
authors: Department of Biotechnology, Jinan University, Guangzhou, China.
authors: Hongling
authors: H
authors: Ma
authors: Wenbin
authors: W
authors: Zhong
authors: Yingliang
authors: Y
authors: Jiang
authors: Coralie
authors: C
authors: Fontaine
authors: Shiqian
authors: S
authors: Li
authors: Jiangnan
authors: J
authors: Fu
authors: Vesa M
authors: VM
authors: Olkkonen
authors: Bart
authors: B
authors: Staels
authors: Daoguang
authors: D
authors: Yan
mesh_terms: D000818:Animals; D001011:Aorta / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D001018:Aortic Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors; D005838:Genotype; D018836:Inflammation Mediators / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics; D008055:Lipids / Q000097:blood; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1 / Q000172:deficiency* / Q000235:genetics; D010641:Phenotype; D034622:RNA Interference; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics; D014161:Transduction, Genetic
chemical_list: D018836:Inflammation Mediators; D008055:Lipids; C498262:Nr1d1 protein, mouse; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; D011973:Receptors, LDL
keywords: Rev‐erbα; atherosclerosis; macrophages
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