Mycophenolic acid inhibits oleic acid-induced vascular smooth muscle cell activation by inhibiting cellular reactive oxygen species.
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.
Ahn
Hyung Joon
HJ
Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea.
Park
Jehyun
J
Song
Jae Sook
JS
Ju
Man Ki
MK
Kim
Myoung Soo
MS
Ha
Hunjoo
H
Song
Ki Ho
KH
Kim
Yu Seun
YS
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*
D005353:Fibronectins; D017382:Reactive Oxygen Species; D019301:Oleic Acid; D009173:Mycophenolic Acid; D000111:Acetylcysteine