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Mycophenolic Acid Inhibits Oleic Acid–Induced Vascular Smooth Muscle Cell Activation by Inhibiting Cellular Reactive Oxygen Species

 Hyung Joon Ahn  ;  Jehyun Park  ;  Yu Seun Kim  ;  Ki Ho Song  ;  Hunjoo Ha  ;  Myoung Soo Kim  ;  Man Ki Ju  ;  Jae Sook Song 
 TRANSPLANTATION, Vol.84(5) : 634-638, 2007 
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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.
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1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Orofacial Pain and Oral Medicine (구강내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Medical Education (의학교육학과) > 1. Journal Papers
Yonsei Authors
Kim, Myoung Soo(김명수) ORCID logo https://orcid.org/0000-0002-8975-8381
Kim, Yu Seun(김유선) ORCID logo https://orcid.org/0000-0002-5105-1567
Park, Je Hyun(박제현)
Song, Jae Sook(송재숙)
Ahn, Hyoung Joon(안형준)
Joo, Man Ki(주만기) ORCID logo https://orcid.org/0000-0002-4112-7003
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