title: The antioxidant N-acetylcysteine promotes atherosclerotic plaque stabilization through suppression of RAGE, MMPs and NF-κB in ApoE-deficient mice.
abstract: OBJECTIVE
  N-acetylcysteine (NAC) has antioxidant and anti-inflammatory properties. To explore the mechanisms underlying atherosclerotic plaque stabilization induced by NAC, we examined the effects of NAC administration in apoE-deficient mice on the expression of the receptor of advanced glycation end products (RAGE), matrix metalloproteinases (MMPs) and the activation of nuclear factor kappa B (NF-κB) in atherosclerotic plaques.
  
  
  METHODS
  10-week-old ApoE(-/-) mice fed with atherogenic diet were treated with NAC (200 mg/kg/ day) for 8 weeks. Serum lipid, glucose and malondialdehyde (MDA) were detected. The size and composition of atherosclerotic plaques were measured by en face analysis, Movat staining, immunofluorescence and immunohistochemistry, respectively. Reactive oxygen species (ROS) generation in aortic root was tested by DHE staining. The levels of vascular cell adhesion molecule-1(VCAM-1), NF-κB, phosphor-NF-κB, I-κB, phosphor-I-κB, RAGE, MMP2 and MMP9 in descending arteries were analyzed by Western blot.
  
  
  RESULTS
  ApoE(-/-) mice administrated with NAC displayed reduced serum MDA level and impaired ROS generation in aortic root. However, NAC did not affect the levels of plasma glucose, lipids and the size of atherosclerotic lesions. Analysis of plaque composition showed decreased amounts of macrophages, lipid deposition, but not smooth muscle cells, and increased collagen content in atherosclerotic lesions in apoE(-/-) mice administered with NAC. Moreover, we found that NAC down-regulated the expression of VCAM-1, MMP2 and MMP9, accompanied by inhibition of NF-κB activation and reduced expression of RAGE.
  
  
  CONCLUSIONS
  In the present study, we show novel data to suggest that NAC promotes atherosclerotic plaque stabilization through suppression of RAGE, MMPs and NF-κB in apoE(-/-) mice.
authors.affiliation: Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Lu
authors.forename: Weiwei
authors.initials: W
authors.lastname: Qin
authors.forename: Tao
authors.initials: T
authors.lastname: Shen
authors.forename: Lin
authors.initials: L
authors.lastname: Dou
authors.forename: Yong
authors.initials: Y
authors.lastname: Man
authors.forename: Shu
authors.initials: S
authors.lastname: Wang
authors.forename: Chuanshi
authors.initials: C
authors.lastname: Xiao
authors.forename: Jian
authors.initials: J
authors.lastname: Li
mesh_terms: D000111:Acetylcysteine / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000009:adverse effects*; D001057:Apolipoproteins E / Q000502:physiology*; D001786:Blood Glucose / Q000378:metabolism; D004036:Diet, Atherogenic; D005455:Fluorescent Antibody Technique; D016166:Free Radical Scavengers / Q000633:toxicity; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism*; D058226:Plaque, Atherosclerotic / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D001057:Apolipoproteins E; D001786:Blood Glucose; D016166:Free Radical Scavengers; D017127:Glycation End Products, Advanced; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D020782:Matrix Metalloproteinases; D000111:Acetylcysteine