Homocysteine-impaired angiogenesis is associated with VEGF/VEGFR inhibition
- Authors
- Zhang, Q., Li, Q., Chen, Y., Huang, X., Yang, I.H., Cao, L., Wu, W.K., and Tan, H.M.
- ID
- ZDB-PUB-120604-4
- Date
- 2012
- Source
- Frontiers in bioscience : a journal and virtual library 4: 2525-2535 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Base Sequence
- Cell Cycle
- Cell Movement
- Cell Proliferation
- Cells, Cultured
- DNA Primers
- Endothelium, Vascular/cytology
- Endothelium, Vascular/metabolism
- Homocysteine/physiology*
- Humans
- Neovascularization, Physiologic*
- RNA, Messenger/genetics
- Real-Time Polymerase Chain Reaction
- Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors*
- Vascular Endothelial Growth Factor A/antagonists & inhibitors*
- Zebrafish
- PubMed
- 22652658 Full text @ Front. Biosci.
This study investigated the effects of homocysteine (Hcy) on angiogenesis in cultured human umbilical vein endothelial cells (HUVEC) and zebrafish embryos. We found that Hcy (50 micro mol/L) significantly decreased cell numbers, viability, and induced a G1/S arrest in HUVEC in the presence of adenosine (Ade, 50 micro mol/L). Hcy, in combination with Ade, reduced migration and suppressed tube-like formation on Matrigel in HUVEC. Further, Hcy reduced subintestinal vessel formation in zebrafish embryos. Interestingly, Hcy-induced inhibitory effects on cell growth, migration, tube-like formation, and vessel formation in HUVEC and zebra fish embryos were abolished by the supplement of recombinant VEGF (10ng/ml). Finally, Hcy in combination with Ade reduced the mRNA levels of VEGF, VEGFR-1, VEGFR-2, and attenuated protein levels of VEGF, ERK1/2 and Akt. The present study suggests that Hcy inhibits angiogenesis, and that the mechanism anti-angiogenic effects of Hcy may be through VEGF/VEGFR, Akt, and ERK1/2 inhibition.