title: Mycophenolic acid inhibits oleic acid-induced vascular smooth muscle cell activation by inhibiting cellular reactive oxygen species.
abstract: BACKGROUND
  Vascular smooth muscle cell (VSMC) proliferation and matrix protein accumulation play important roles in the development and progression of chronic allograft vasculopathy. Mycophenolic acid (MPA) inhibits various types of mesenchymal cell proliferation and cellular reactive oxygen species (ROS) are involved in the anti-proliferative effect of MPA. In this study, we investigated the effects of MPA on oleic acid (OA)-induced VSMC proliferation and the role of ROS in this process.
  
  
  METHODS
  Primary VSMCs from Sprague-Dawley rats were stimulated with 100 microM OA, with or without MPA (0.1- 10 microM) or 5 mM N-acetylcysteine (NAC) for one hour prior to the addition of OA. Cell proliferation was measured by methylthiazoletetrazolium (MTT) assays, proliferating cell nuclear antigen (PCNA) expression, and fibronectin secretion by Western blot analysis, and dichlorofluorescein (DCF)-sensitive cellular ROS by fluorescence-activated cell scanning (FACS).
  
  
  RESULTS
  OA (100 microM) increased cell proliferation, as measured by MTT (by 1.6-fold), PCNA expression, fibronectin secretion, and cellular ROS (by 1.6-fold). Treatment with MPA dose-dependently inhibited OA-induced VSMC proliferation, fibronectin secretion, and cellular ROS. Treatment with 5 mM NAC also inhibited OA-induced rat VSMC activation.
  
  
  CONCLUSIONS
  These results suggest that MPA inhibits OA-induced VSMC proliferation and matrix protein synthesis partially by inhibiting cellular ROS.
authors: Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea.
authors: Hyung Joon
authors: HJ
authors: Ahn
authors: Jehyun
authors: J
authors: Park
authors: Jae Sook
authors: JS
authors: Song
authors: Man Ki
authors: MK
authors: Ju
authors: Myoung Soo
authors: MS
authors: Kim
authors: Hunjoo
authors: H
authors: Ha
authors: Ki Ho
authors: KH
authors: Song
authors: Yu Seun
authors: YS
authors: Kim
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects; D005353:Fibronectins / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D009173:Mycophenolic Acid / Q000494:pharmacology*; D019301:Oleic Acid / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D005353:Fibronectins; D017382:Reactive Oxygen Species; D019301:Oleic Acid; D009173:Mycophenolic Acid; D000111:Acetylcysteine