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The neurotrophic pyrimidine heterocyclic compound MS-818 promotes the angiogenesis induced by basic FGF
S Yasuhara1, S Kashiwagi, H Ito
1Department of Neurosurgery, Yamaguchi University School of Medicine, Japan.
Abstract:
The chorioallantoic membrane (CAM) assay is a bioassay used widely for testing angiogenic activities of compounds. In the present study, we used this assay to explore the gross and micropathological effects of 2-piperadino-6-methyl-5-oxo-5,6-dihydro (7H) pyrrolo[3,4-d] pyrimidine maleate (MS-818) in combination with basic fibroblast growth factor (bFGF). Light microscopy revealed that application of 1, 10 and 100 ng/ml bFGF to the CAM induced a concentration-dependent increase in the number of new blood vessels, whereas application of 0.01, 0.1 and 1.0 mM MS-818 did not increase angiogenesis significantly. The combinations of 10 ng/ml bFGF with 0.1, 0.1 and 1.0 mM MS-818 showed significantly greater angiogenic effects than 10 ng/ml bFGF alone. However, 1 and 100 ng/ml bFGF in combination with these concentrations of MS-818 showed no additive effects. Histologically, numerous mononuclear cells became present in the mesodermal stroma, especially around the capillaries, when MS-818 alone and with bFGF was applied to the CAM. The new vessels formed in response to MS-818 plus bFGF were smaller than those formed with bFGF alone. These results suggest that, in the CAM assay system, MS-818 promoted angiogenesis effectively when the concentration or activity of the angiogenic factor (bFGF) was potentiated by MS-818 at a real optimal level.
Insights
The study found that MS-818 enhances angiogenesis, particularly when combined with basic fibroblast growth factor (bFGF) at optimal levels in the chorioallantoic membrane (CAM) assay. MS-818 alone did not significantly promote new blood vessel growth.
Area of Science:
- Angiogenesis research
- Pharmacological studies
- Bioassay development
Background:
- The chorioallantoic membrane (CAM) assay is a standard method for evaluating compounds' angiogenic potential.
- Understanding how compounds interact with growth factors is crucial for developing pro-angiogenic therapies.
Purpose of the Study:
- To investigate the effects of MS-818, alone and in combination with basic fibroblast growth factor (bFGF), on angiogenesis using the CAM assay.
- To explore the gross and micropathological changes induced by MS-818 and bFGF.
Main Methods:
- Utilized the chorioallantoic membrane (CAM) assay for angiogenesis testing.
- Applied varying concentrations of bFGF and MS-818, both individually and in combination.
- Analyzed results using light microscopy and histological examination.
Main Results:
- bFGF alone induced a dose-dependent increase in blood vessel formation.
- MS-818 alone did not significantly promote angiogenesis.
- Combinations of 10 ng/ml bFGF with 0.1-1.0 mM MS-818 showed enhanced angiogenic effects compared to bFGF alone.
- Higher bFGF concentrations (1 and 100 ng/ml) with MS-818 did not yield additive effects.
- MS-818 application led to mononuclear cell infiltration and smaller new vessel formation compared to bFGF alone.
Conclusions:
- MS-818 can effectively promote angiogenesis in the CAM assay when potentiated by bFGF at an optimal level.
- The findings suggest a synergistic interaction between MS-818 and bFGF under specific concentration conditions.
- MS-818's mechanism involves mononuclear cell recruitment and influences the morphology of newly formed vessels.