Homocysteine-impaired angiogenesis is associated with VEGF/VEGFR inhibition

Front Biosci (Elite Ed). 2012 Jun 1;4(7):2525-35. doi: 10.2741/e563.

Abstract

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 micromol/L) significantly decreased cell numbers, viability, and induced a G1/S arrest in HUVEC in the presence of adenosine (Ade, 50 micromol/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 (10 ng/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.

Publication types

  • Research Support, Non-U.S. Gov't

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

Substances

  • DNA Primers
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • Homocysteine
  • Receptors, Vascular Endothelial Growth Factor