Inhibitory Effects of A-8 on Abnormal Rat Aortic Vascular Smooth Muscle Cell Proliferation

동맥혈관 평활근세포 증식에 대한 오보바톨 유도체(A-8)의 억제효과

  • Lim, Yong (Department of Clinical Laboratory Science, Dong-eui University) ;
  • Lee, Mi-Yea (Department of Social Welfare, World Cyber College) ;
  • Tudev, Munkhtsetseg (College of Pharmacy and CBITRC, Chungbuk National University) ;
  • Park, Eun-Seok (College of Pharmacy and CBITRC, Chungbuk National University) ;
  • Jung, Jae-Kyung (College of Pharmacy and CBITRC, Chungbuk National University) ;
  • Yun, Yeo-Pyo (College of Pharmacy and CBITRC, Chungbuk National University)
  • Received : 2010.12.24
  • Accepted : 2011.04.11
  • Published : 2011.04.30

Abstract

Abnormal proliferation of vascular smooth muscle cells (VSMCs) plays an important role in the development and progression of proliferative cardiovascular diseases, including hypertension and atherosclerosis. To find antiproliferative agent (A)-8 had inhibitory effect on VSMCs proliferation. Therefore, we examined the antiproliferative effect of A-8, a newly synthesized obovatol derivative. To investigate the antiproliferative effect of A-8, we examined cell counting and [$^3H$]-thymidine incorporation assays. The pre-incubation of A-8 (1~4 ${\mu}M$) significantly inhibited proliferation and DNA synthesis of 5% fetal bovine serum (FBS)-stimulated rat aortic VSMCs in concentration-dependent manner. Whereas, A-8 did not show any cytotoxicity in rat aortic VSMCs in this experimental condition by WST-1 assay. In addition, A-8 significantly inhibited 5% FBS-induced cell cycle progression in rat aortic VSMCs. These results show that A-8 may be developed as a potential antiproliferative agent for treatment of angioplasty restenosis and atherosclerosis. Furthermore, A-8 should be examined for further clinical application either as a single agent or in combination with other angioplasty restenosis or atherosclerosis agents.

Keywords

References

  1. Abelson, P. H. : Flaws in risk assessments. Science 270, 215 (1995). https://doi.org/10.1126/science.270.5234.215
  2. Lusis, A. J. : Atherosclerosis. Nature 407, 233 (2000). https://doi.org/10.1038/35025203
  3. Garas, S. M., Huber, P. and Scott, N. A. : Overview of therapies for prevention of restenosis after coronary interventions. Pharmacol. Ther. 92, 165 (2001). https://doi.org/10.1016/S0163-7258(01)00168-1
  4. Kearney, M., Ann, P., Laura, H., Douglas, W., Vicente, A., Robert, S., Kenneth, R. and Jeffrey, M. I. : Histopathology of instent restenosis in patients with peripheral artery disease. Circulation 95, 1998 (1997). https://doi.org/10.1161/01.CIR.95.8.1998
  5. Schwartz, S. M. : Smooth muscle migration in atherosclerosis and restenosis. J. Clin. Invest. 99, 2814 (1997). https://doi.org/10.1172/JCI119472
  6. Doevendans, P. A. and Eys, G. : Smooth muscle cells on the move: the battle for actin. Cardiovasc. Res. 54, 499 (2002). https://doi.org/10.1016/S0008-6363(02)00395-4
  7. Lee, M. S., Yang, J. E., Choi, E. H., In, J. K., Lee, S. Y., Lee, H., Hong, J. T., Lee, H. W., Suh, Y. G. and Jung, J. K. : Synthesis of obovatol derivatives and their preliminary evaluation as antitumor agents. Bull. Korean Chem. Soc. 28, 1601 (2007). https://doi.org/10.5012/bkcs.2007.28.9.1601
  8. Ross, R. : The pathogenesis: a perspective for the 1990s. Nature 362, 801 (1993). https://doi.org/10.1038/362801a0
  9. Braun-Dullaeus, R. C., Mann, M. J., Sedding, D. G., Sherwood, S. W., von der Leyen, H. E. and Dzau, V. J. : Cell cycledependent regulation of smooth muscle cell activation. Arterioscler. Thromb. Vasc. Biol. 24, 845 (2004). https://doi.org/10.1161/01.ATV.0000125704.28058.a2