title: Xiaoxianggou attenuates atherosclerotic plaque formation in endogenous high Ang II ApoE(-/-) mice via the inhibition of miR-203 on the expression of Ets-2 in endothelial cells.
abstract: BACKGROUND
  Atherosclerosis is a chronic immune-inflammatory disorder and one of the leading causes responsible for cardiovascular morbidity and mortality. Traditional Chinese medicine treatment with multi-targets has shown prospects for the therapeutic effect on atherosclerosis. Thus, this study aims to investigate whether xiaoxianggou has benefit for reducing the atherosclerotic plaque area in endogenous high Ang II ApoE(-/-) mice and investigated the underlying mechanisms.
  
  
  METHODS
  Endogenous high Ang II ApoE(-/-) mice model was generated by using two kidney one clip (2K1C). All mice were treated by intragastric administration with xiaoxianggou two times a week for 16 weeks. En face plaque area was analyzed by oil-red O staining. Serum anti-OxLDL antibodies were measured by ELISA assay. Expression of miR-203 and Ets-2 were evaluated using qRT-RCR and western blotting analysis, respectively.
  
  
  RESULTS
  This study revealed that xiaoxianggou treatment dose-dependently reduced the atherosclerotic plaque area and serum autoantibodies against oxLDL, elevated miR-203 expression and reduced Ets-2 expression in endogenous high Ang II ApoE(-/-) mice. In primary arterial ECs, Xiaoxianggou reverses the reduced miR-203 expression and the elevated Ets-2 expression induced by AngII, which was further recovered by miR-203 inhibitor. Additionally, miR-203 regulated the expression of Ets-2 by targeting Ets-2-3' UTR. Moreover, miR-203 inhibitor reversed the reduction of atherosclerotic lesion area induced by Xiaoxianggou.
  
  
  CONCLUSIONS
  These findings present that xiaoxianggou plays an anti-atherosclerotic role in endogenous high Ang II ApoE(-/-) mice model, which is partly due to its antioxidant actions against atherosclerosis and the inhibition of miR-203 on the expression of Ets-2 in endothelial cells.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, 310003, China.
authors.forename: Wencheng
authors.initials: W
authors.lastname: Nie
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, 310003, China.
authors.forename: Xiaoqun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, 310003, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, 310003, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, 310003, China.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, 310003, China.
authors.forename: Fangyan
authors.initials: F
authors.lastname: Fan
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, 310003, China. Electronic address: zhujianhua2006@hotmail.com.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhu
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000378:metabolism; D001323:Autoantibodies / Q000097:blood; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D008077:Lipoproteins, LDL / Q000276:immunology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D050787:Proto-Oncogene Protein c-ets-2 / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D001057:Apolipoproteins E; D001323:Autoantibodies; D004365:Drugs, Chinese Herbal; C494070:Ets2 protein, mouse; D008077:Lipoproteins, LDL; C575934:MIRN203 microRNA, mouse; D035683:MicroRNAs; D050787:Proto-Oncogene Protein c-ets-2; C099252:oxidized low density lipoprotein; C000613729:xiaoxianggou; D000804:Angiotensin II
keywords: Atherosclerotic plaque formation; Ets-2; Xiaoxianggou; miR-203