Mycophenolic acid가 올레산으로 유도한 흰쥐 혈관 평활근 세포의 증식에 미치는 영향

Abstract

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 100μM. MPA 0.1∼10μM 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 100μM 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 1μM inhibited OA- induced VSMC proliferation and cellular ROS in a dosedependent 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.