Vascular smooth muscle cell (VSMC) proliferation, migration, and matrix protein accumulation play important roles in the development and progression of vascular disease including diabetic vascular complications and chronic allograft vasculopathy. Mycophenolic acid (MPA) inhibits various mesenchymal cell proliferation and matrix protein accumulation and reactive oxygen species (ROS). In this study, we investigated the effects of MPA on high glucose (HG)-induced fibronectin secretion and the role of ROS in rat VSMCs. Primary cultured rat VSMCs from Sprague-Dawley rats were exposed for 1 hour before stimulation with media containing 5.6 mmol/L glucose (low glucose [LG]), 30 mmol/L mannitol (M), or 30 mmol/L glucose (HG) with or without MPA (0.1-10 μmol/L) or N-acetylcysteine (NAC; 5 mmol/L). Fibronectin secretion was measured by Western blot analysis and dichlorofluorescein (DCF)-sensitive cellular ROS by flow cytometry. HG significantly increased fibronectin secretion by 1.7-fold. The increment of DCF-sensitive cellular ROS was 1.5-fold at 1 hour by HG. MPA at concentrations above 1 μmol/L effectively inhibited HG-induced fibronectin secretion and cellular ROS in a dose-dependent manner. NAC at 5 mmol/L also inhibited HG-induced rat VSMC activation. These results suggested that MPA inhibits HG-induced VSMC activation partially through inhibiting cellular ROS.
|Number of pages||3|
|Publication status||Published - 2008 Mar 1|
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