Homocysteine-impaired angiogenesis is associated with VEGF/VEGFR inhibition.
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.
Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
Quan
Q
Zhang
Qian
Q
Li
Yu
Y
Chen
Xiao
X
Huang
Irene Hwa
IH
Yang
Lu
L
Cao
Wei-Kang
WK
Wu
Hong-Mei
HM
Tan
D000818:Animals; D001483:Base Sequence; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D006710:Homocysteine / Q000502:physiology*; D006801:Humans; D018919:Neovascularization, Physiologic; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D015027:Zebrafish
D017931:DNA Primers; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D006710:Homocysteine; D040262:Receptors, Vascular Endothelial Growth Factor