PUBLICATION

Caffeine Inhibits Direct and Indirect Angiogenesis in Zebrafish Embryos

Authors
Basnet, R.M., Zizioli, D., Muscò, A., Finazzi, D., Sigala, S., Rossini, E., Tobia, C., Guerra, J., Presta, M., Memo, M.
ID
ZDB-PUB-210603-7
Date
2021
Source
International Journal of Molecular Sciences   22(9): (Journal)
Registered Authors
Presta, Marco, Tobia, Chiara
Keywords
FGF2, angiogenesis, caffeine, embryonic vascular development, methylxanthines, zebrafish
MeSH Terms
  • Animals
  • Caffeine/pharmacology*
  • Cell Line, Tumor
  • Embryo, Nonmammalian
  • Embryonic Development/drug effects
  • Fibroblast Growth Factor 2/genetics*
  • Gene Expression Regulation, Developmental/drug effects
  • Heterografts
  • Humans
  • In Situ Hybridization
  • Neovascularization, Pathologic/drug therapy*
  • Neovascularization, Pathologic/genetics
  • Neovascularization, Pathologic/pathology
  • Neovascularization, Physiologic/drug effects*
  • Neovascularization, Physiologic/genetics
  • Zebrafish/genetics
  • Zebrafish/growth & development
PubMed
34063734 Full text @ Int. J. Mol. Sci.
Abstract
In this study, we report the effects of caffeine on angiogenesis in zebrafish embryos both during normal development and after exposure to Fibroblast Growth Factor 2 (FGF2). As markers of angiogenesis, we measured the length and width of intersegmental vessels (ISVs), performed whole-mount in situ hybridization with fli1 and cadh5 vascular markers, and counted the number of interconnecting vessels (ICVs) in sub-intestinal venous plexus (SIVP). In addition, we measured angiogenesis after performing zebrafish yolk membrane (ZFYM) assay with microinjection of fibroblast growth factor 2 (FGF2) and perivitelline tumor xenograft assay with microinjection of tumorigenic FGF2-overexpressing endothelial (FGF2-T-MAE) cells. The results showed that caffeine treatment causes a shortening and thinning of ISVs along with a decreased expression of the vascular marker genes and a decrease in the number of ICVs in the SIVP. Caffeine was also able to block angiogenesis induced by exogenous FGF2 or FGF2-producing cells. Overall, our results are suggestive of the inhibitory effect of caffeine in both direct and indirect angiogenesis.
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