title: Berberine activates peroxisome proliferator-activated receptor gamma to increase atherosclerotic plaque stability in Apoe-/-mice with hyperhomocysteinemia.
abstract: OBJECTIVE
  An elevated level of plasma homocysteine has long been suspected as a metabolic risk factor for the development of atherosclerotic vascular diseases in diabetes. Berberine (BBR) has several preventive effects on cardiovascular diseases. The effects of BBR on atherosclerotic plaque stability increased by homocysteine thiolactone (HTL) remain unknown.
  
  
  METHODS
  The model of atherosclerotic vulnerable plaque was induced by placing a collar around the carotid artery in Apoe-/-mice. Endothelium-dependent relaxation was assayed by organ chamber.
  
  
  RESULTS
  Homocysteine thiolactone (50 mg/kg/day, 8 weeks) reduced the atherosclerotic plaque stability in the carotid artery of Apoe-/-mice, which was reversed by BBR administration (1.0 g/kg/day). In vivo and ex vivo experiments showed that HTL dramatically reduced acetylcholine-induced endothelium-dependent relaxation and superoxide dismutase activity, and increased malondialdehyde content, which were inhibited by BBR. Importantly, all effects induced by BBR were abolished by GW9662, an antagonist of peroxisome proliferator-activated receptor-γ. Incubation of cultured endothelial cells with HTL significantly reduced cell viabilities and enhanced production of reactive oxygen species. Pretreatment of cells with BBR dose-dependently reversed HTL-induced detrimental effects, which were GW9662-reversible.
  
  
  CONCLUSIONS
  Berberine increases atherosclerotic plaque stability in hyperhomocysteinemia mice, which is related to the activation of peroxisome proliferator-activated receptor-γ and subsequent suppression of oxidative stress in endothelial cells.
authors.affiliation: China-Japan Union Hospital, Jilin University, Changchun, China.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Li
authors.affiliation: China-Japan Union Hospital, Jilin University, Changchun, China.
authors.forename: Chengyan
authors.initials: C
authors.lastname: He
authors.affiliation: China-Japan Union Hospital, Jilin University, Changchun, China.
authors.forename: Jingying
authors.initials: J
authors.lastname: Wang
authors.affiliation: Tumor Hospital of Jilin Province, The Second Hospital of Jilin University, Changchun, China.
authors.forename: Xiaoou
authors.initials: X
authors.lastname: Li
authors.affiliation: China-Japan Union Hospital, Jilin University, Changchun, China.
authors.forename: Zhaowei
authors.initials: Z
authors.lastname: Yang
authors.affiliation: China-Japan Union Hospital, Jilin University, Changchun, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Sun
authors.affiliation: China-Japan Union Hospital, Jilin University, Changchun, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Fang
authors.affiliation: Central Laboratory, The Second Hospital of Jilin University, Changchun, China. liu_ning@jlu.edu.cn.
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D001599:Berberine / Q000008:administration & dosage*; D002339:Carotid Arteries / Q000187:drug effects / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006710:Homocysteine / Q000008:administration & dosage / Q000031:analogs & derivatives; D020138:Hyperhomocysteinemia / Q000139:chemically induced* / Q000150:complications; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000187:drug effects; D047495:PPAR gamma / Q000378:metabolism*; D058226:Plaque, Atherosclerotic / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control*
chemical_list: D001057:Apolipoproteins E; D047495:PPAR gamma; D001599:Berberine; D006710:Homocysteine; C007957:homocysteine thiolactone
keywords: Atherosclerosis; Berberine; Peroxisome proliferator-activated receptor-γ