Anti-angiogenic drug AGM1470 suppresses smooth muscle cell migration induced by endothelial PDGF

Eur J Vasc Endovasc Surg. 1997 Oct;14(4):290-8. doi: 10.1016/s1078-5884(97)80241-9.

Abstract

Objectives: To examine the effects of the anti-angiogenic drug AGM1470 on smooth muscle cell (SMC) migration activity stimulated by endothelial cell (EC)-derived mitogen.

Materials and methods: Study 1; EC's were cultured under pulsatile flow using MCDB151 medium. From the supernatant of these EC dishes we devised two types of conditioned medium; anti-PDGF(+) containing 10 micrograms/ml anti-PDGF antibody, and anti-PDGF(-) containing no antibody. SMC's were cultured using both media. Study 2; EC's were cultured under the same conditions using both types of medium; MCDB151 medium containing 10 ng/ml AGM1470, and MCDB151 medium alone. After the AGM1470 concentration had been adjusted to 10 ng/ml, SMC's were cultured using each medium; AGM-exposed EC and AGM-non-exposed EC. SMC colony spreading distances were measured as an index of mitogenic activity for 4 days.

Results: Study 1; the anti-PDGF(-) group showed an apparently greater spreading distance than the anti-PDGF(+) group. Study 2; the AGM-non-exposed EC group showed a significantly greater spreading distance than the AGM-exposed EC group. However, MTT assay revealed no differences in proliferation between the two groups.

Conclusion: AGM1470 suppresses the EC production of this PDGF-like mitogen as well as SMC migration activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Cell Movement / drug effects*
  • Cells, Cultured
  • Culture Media
  • Cyclohexanes
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiology
  • Hemodynamics
  • Humans
  • Mitogens / pharmacology*
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / physiology
  • Neovascularization, Physiologic / drug effects*
  • O-(Chloroacetylcarbamoyl)fumagillol
  • Pulsatile Flow / drug effects
  • Sesquiterpenes / pharmacology*
  • Stress, Mechanical
  • Thymidine Phosphorylase / pharmacology*

Substances

  • Culture Media
  • Cyclohexanes
  • Mitogens
  • Sesquiterpenes
  • Thymidine Phosphorylase
  • O-(Chloroacetylcarbamoyl)fumagillol