Mycophenolic acid inhibits oleic acid-induced vascular smooth muscle cell activation by inhibiting cellular reactive oxygen species

Hyung Joon Ahn, Jehyun Park, Jae Sook Song, Man Ki Ju, Myoung Soo Kim, Hunjoo Ha, Ki Ho Song, YuSeun Kim

Research output: Contribution to journalArticle

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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 languageEnglish
Pages (from-to)634-638
Number of pages5
JournalTransplantation
Volume84
Issue number5
DOIs
Publication statusPublished - 2007 Sep 1

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Mycophenolic Acid
Oleic Acid
Vascular Smooth Muscle
Smooth Muscle Myocytes
Reactive Oxygen Species
Cell Proliferation
Fibronectins
Proliferating Cell Nuclear Antigen
Acetylcysteine
Allografts
Sprague Dawley Rats
Proteins
Fluorescence
Western Blotting

All Science Journal Classification (ASJC) codes

  • Transplantation

Cite this

Ahn, Hyung Joon ; Park, Jehyun ; Song, Jae Sook ; Ju, Man Ki ; Kim, Myoung Soo ; Ha, Hunjoo ; Song, Ki Ho ; Kim, YuSeun. / Mycophenolic acid inhibits oleic acid-induced vascular smooth muscle cell activation by inhibiting cellular reactive oxygen species. In: Transplantation. 2007 ; Vol. 84, No. 5. pp. 634-638.
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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.",
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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, YuSeun.

In: Transplantation, Vol. 84, No. 5, 01.09.2007, p. 634-638.

Research output: Contribution to journalArticle

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, YuSeun

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.

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