J Korean Soc Transplant.
2003 Jun;17(1):1-6.
Effect of Mycophenolic Acid and Rapamycin on the Proliferation and Collagen Synthesis of the Vascular Smooth Muscle Cell of Rat
- Affiliations
-
- 1The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea.
- 2Department of Surgery, Yonsei University College of Medicine, Seoul, Korea. yukim@yumc.yonsei.ac.kr
- 3Department of Surgery, Yonsei University Wonju College of Medicine, Wonju, Korea.
- 4Hyonam Kidney Laboratory, Soon Chun Hyang University, Seoul, Korea.
Abstract
- PURPOSE
Vascular smooth muscle cell (VSMC) proliferation and extracellular matrix protein accumulation play important roles in chronic allograft vasculopathy. Mycophenolic acid (MPA) or rapamycin (RPM) was reported to inhibit VSMC proliferation in vitro and in vivo. However, effects of MPA or RPM on collagen synthesis of VSMCs, and the combined effects of MPA and RPM treatment on VSMC proliferation are not yet reported.
METHODS
VSMCs isolated from the aorta of Sprague-Dawley rats were cultured with EMEM supplemented with 10% fetal bovine serum and insulin/ transferrin. Growth arrested and synchronized cells were pretreated with test drugs (alone or combination of various concentrations of MPA and RPM) 1 hour before the addition of 10 ng/ml PDGF. Cell proliferation was assessed by [H3]- thymidine incorporation, and collagen synthesis by [H3]- proline incorporation.
RESULTS
PDGF increased cell proliferation and collagen synthesis by 3.4- and 2.1-fold, respectively, compared to control. MPA at above 100 nM or RPM at above 1 nM effectively inhibited PDGF-induced cell proliferation and collagen synthesis. The IC50 of MPA or RPM against PDGF-stimulated cell proliferation was between 100 nM and 1 micrometer or between 1 nM and 10 nM, respectively. The combination of MPA and RPM showed additive effects on PDGF-induced VSMC proliferation in a multiple regression analysis (R2=0.508, P<0.05).
CONCLUSION
The present study demonstrated that MPA or RPM significantly inhibited PDGF-induced VSMC proliferation. These independent phenomena were well maintained as suggested by additive effects after combination treatment. PDGF-induced collagen synthesis was also effectively suppressed by the treatment of MPA or RPM.
- Full Text Links
-
- Actions
-
Cited
- CITED
-
- Close
- Share
-
- Similar articles
-
- Effect of Cyclosporine, Mycophenolic Acid, and Rapamycin on the Proliferation of Rat Aortic Vascular Smooth Muscle Cells: in Vitro Study
- Effects of Mycophenolic Acid and Rapamycin on PDGF-induced Mesangial Cell Proliferation and Extracellular Matrix Production
- Effect of Mycophenolic Acid and Rapamycin on the Proliferation of Glomerular Mesangial Cell of Rat
- Effects of Mycophenolic Acid on Oleic Acid- induced Rat Vascular Smooth Muscle Cell Proliferation
- Antiproliferative Effect of Lovastatin on Vascular Smooth Muscle Cell
