Cardiovascular disease is associated with a multitude of pathophysiologic conditions, including vascular smooth muscle cell (VSMC) proliferation in response to vessel injury. Diethylstilbestrol (DES) was previously prescribed for at-risk pregnancies to prevent abortion, miscarriage, and premature labor. Our aim in this study was to elucidate the effects and molecular mechanism of DES on proliferation and cell cycle progression of platelet-derived growth factor (PDGF)-BB-stimulated rat aortic VSMCs. Treating the cells with DES (1-7 μM) dramatically inhibited cell proliferation in a dose-dependent manner without any cytotoxic effects. In addition, DES blocked cell cycle progression from PDGF-BB-stimulated cells, which we found was related to down-regulation of the cell cycle regulatory factors, cyclin D1, and cyclin E. Our data demonstrate that DES inhibits rat aortic VSMC proliferation and cell cycle progression through regulation of cell cycle-related proteins. Therefore, our observations may explain, in part, the mechanistic basis underlying the therapeutic effects of DES in cardiovascular disease.
Bibliographical noteFunding Information:
Acknowledgments The authors are grateful to Dr. Sang-Hyun Sung (Seoul National University, Seoul, Korea) for providing us with DES. This research was supported by Industrialization Support Program for Bio-technology of Agriculture and Forestry (810007-03-1-SB220), Ministry for Food, Agriculture, Forestry and Fisheries, Republic of Korea.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Clinical Biochemistry
- Cell Biology