J Korean Surg Soc.
2007 Mar;72(3):171-176.
Effects of Mycophenolic Acid on Oleic Acid- induced Rat Vascular Smooth Muscle Cell Proliferation
- Affiliations
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- 1Department of Surgery, Yonsei University College of Medicine, Korea. yukim@yumc.yonsei.ac.kr
- 2The Research Institute for Transplantation, Yonsei University College of Medicine, Korea.
- 3Ewha Womans University College of Pharmacy, Korea.
- 4Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea.
Abstract
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PURPOSE: Vascular smooth muscle cell (VSMC) proliferation plays an important role in the development and progression of chronic allograft vasculopathy. Mycophenolic acid (MPA) inhibits various mesenchymal cell proliferation, and reactive oxygen species (ROS) are involved in the anti-pro-liferative effect of MPA. In this study, we investigated the effects of MPA on oleic acid (OA)-induced VSMC proliferation and also the role of ROS in these processes.
METHODS
Primary cultured rat VSMCs from Sprague-Dawley were stimulated with OA 100micrometer. MPA 0.1~10micrometer and N-acetylcystein (NAC) 5 mM were administered 1 hour before adding the OA. Cell proliferation was measured by Methylthiazoletetrazolium (MTT) assay, proliferating cell nuclear antigen (PCNA) expression by Western blot analysis, and dichlorofluorescein (DCF)-sensitive cellular ROS by flow cytometry.
RESULTS
OA at 100micrometer significantly increased MTT level by 1.6-fold as well as PCNA expression at 48 hours in rat VSMCs. OA also induced DCF-sensitive cellular ROS by 1.6-fold at 5 minutes and the increment of cellular ROS remained for up to 1 hour. MPA at above 1micrometer inhibited OA- induced VSMC proliferation and cellular ROS in a dose-ependent manner. NAC 5 mM also inhibited OA-induced rat VSMC activation.
CONCLUSION
These results suggest that MPA inhibits OA-induced VSMC proliferation partially through the inhibition of cellular ROS.
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