Abstract
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 μM OA, with or without MPA (0.1- 10 μM) 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 μM) 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.
| Original language | English |
|---|---|
| Pages (from-to) | 634-638 |
| Number of pages | 5 |
| Journal | Transplantation |
| Volume | 84 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2007 Sep 1 |
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All Science Journal Classification (ASJC) codes
- Transplantation
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Mycophenolic acid inhibits oleic acid-induced vascular smooth muscle cell activation by inhibiting cellular reactive oxygen species. / Ahn, Hyung Joon; Park, Jehyun; Song, Jae Sook; Ju, Man Ki; Kim, Myoung Soo; Ha, Hunjoo; Song, Ki Ho; Kim, Yu Seun.
In: Transplantation, Vol. 84, No. 5, 01.09.2007, p. 634-638.Research output: Contribution to journal › Article
TY - JOUR
T1 - Mycophenolic acid inhibits oleic acid-induced vascular smooth muscle cell activation by inhibiting cellular reactive oxygen species
AU - Ahn, Hyung Joon
AU - Park, Jehyun
AU - Song, Jae Sook
AU - Ju, Man Ki
AU - Kim, Myoung Soo
AU - Ha, Hunjoo
AU - Song, Ki Ho
AU - Kim, Yu Seun
PY - 2007/9/1
Y1 - 2007/9/1
N2 - 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 μM OA, with or without MPA (0.1- 10 μM) 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 μM) 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.
AB - 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 μM OA, with or without MPA (0.1- 10 μM) 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 μM) 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.
UR - http://www.scopus.com/inward/record.url?scp=34548775197&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34548775197&partnerID=8YFLogxK
U2 - 10.1097/01.tp.0000278729.96633.6d
DO - 10.1097/01.tp.0000278729.96633.6d
M3 - Article
C2 - 17876277
AN - SCOPUS:34548775197
VL - 84
SP - 634
EP - 638
JO - Transplantation
JF - Transplantation
SN - 0041-1337
IS - 5
ER -