IMR Press / FBE / Volume 4 / Issue 7 / DOI: 10.2741/E563

Frontiers in Bioscience-Elite (FBE) is published by IMR Press from Volume 13 Issue 2 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article

Homocysteine-impaired angiogenesis is associated with VEGF/VEGFR inhibition

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1 Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
2 Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
3 Department of Pharmacology, Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA, USA
4 Department of Cardiology, Second Hospital of NanChang University, Jiang Xi, China
5 Yale affiliation Primary Care Internal Medicine Residency Program, Yale University School of Medicine, CT, USA

*Author to whom correspondence should be addressed.

Academic Editor: Xiao-Feng Yang

Front. Biosci. (Elite Ed) 2012, 4(7), 2525–2535; https://doi.org/10.2741/E563
Published: 1 June 2012
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 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, Hcyinduced inhibitory effects on cell growth, migration, tubelike 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.

Keywords
Homocysteine
Adenosine
Zebrafish
Angiogenesis
VEGF
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