Anti-angiogenic drug AGM1470 suppresses smooth muscle cell migration induced by endothelial PDGF.
OBJECTIVE
To examine the effects of the anti-angiogenic drug AGM1470 on smooth muscle cell (SMC) migration activity stimulated by endothelial cell (EC)-derived mitogen.


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.


CONCLUSIONS
AGM1470 suppresses the EC production of this PDGF-like mitogen as well as SMC migration activity.
Shigematsu
K
K
Department of Surgery I, University of Tokyo, Japan.
Yasuhara
H
H
Shigematsu
H
H
Muto
T
T
D000704:Analysis of Variance; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D003470:Culture Media; D003510:Cyclohexanes; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics; D006801:Humans; D008934:Mitogens / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D011673:Pulsatile Flow / Q000187:drug effects; D012717:Sesquiterpenes / Q000494:pharmacology*; D013314:Stress, Mechanical; D013939:Thymidine Phosphorylase / Q000494:pharmacology*
D003470:Culture Media; D003510:Cyclohexanes; D008934:Mitogens; D012717:Sesquiterpenes; D013939:Thymidine Phosphorylase; D000077609:O-(Chloroacetylcarbamoyl)fumagillol