Reduced β‑2‑glycoprotein І inhibits hypoxia‑induced retinal angiogenesis in neonatal mice through the vascular endothelial growth factor pathway

Liu,Hongyan; Zhou,Saijun; Denyer,Gareth; Meng,Zhenxing; Chen,Rui; Lv,Lin; Li,Chunjun; Yu,Demin; Yu,Pei

doi:10.3892/mmr.2014.2869

Reduced β‑2‑glycoprotein І inhibits hypoxia‑induced retinal angiogenesis in neonatal mice through the vascular endothelial growth factor pathway

Authors:
- Hongyan Liu
- Saijun Zhou
- Gareth Denyer
- Zhenxing Meng
- Rui Chen
- Lin Lv
- Chunjun Li
- Demin Yu
- Pei Yu
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Affiliations: 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, P.R. China, Department of Biochemistry, The University of Sydney, New South Wales 2006, Australia
Published online on: November 5, 2014 https://doi.org/10.3892/mmr.2014.2869
Pages: 1025-1030

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Abstract

β‑2‑glycoprotein I (β2GPI), also known as apolipoprotein H, is a phospholipid‑binding plasma protein consisting of five homologous repeated units. β2GPI downregulates vascular endothelial growth factor (VEGF) signaling pathways and inhibits angiogenesis in vitro. However, the in vivo roles and effectors of reduced β2GPI and β2GPI in retinal angiogenesis are still not fully understood. In this study, an oxygen‑induced retinopathy model was used to investigate the effects of reduced β2GPI and β2GPI, and to monitor the expression of VEGF, VEGF receptor (VEGFR) 1, VEGFR‑2 and hypoxia‑inducible factor 1 (HIF‑1) mRNA and the phosphorylation of extracellular signal‑regulated kinase (ERK) and Akt. The data showed that both β2GPI and reduced β2GPI inhibited retinal angiogenesis and suppressed the expression of VEGF, VEGFR‑1, VEGFR‑2, HIF‑1, phosphorylated- (p‑) ERK and p‑Akt. The effects of reduced β2GPI were significantly stronger than those of β2GPI. In conclusion, this study showed that β2GPI and reduced β2GPI could inhibit retinal angiogenesis by downregulating the expression of VEGF and its downstream targets. This suggests that β2GPI and reduced β2GPI may have potential anti‑angiogenic activity in vivo.

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