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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Newborn
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Disease Models, Animal
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Down-Regulation
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Extracellular Signal-Regulated MAP Kinases / genetics
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Female
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Hypoxia / pathology*
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Hypoxia-Inducible Factor 1 / genetics
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Hypoxia-Inducible Factor 1 / metabolism*
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Mice
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Mice, Inbred C57BL
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Neovascularization, Pathologic / pathology*
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Oxygen / adverse effects
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Phosphorylation
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Proto-Oncogene Proteins c-akt / genetics
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Proto-Oncogene Proteins c-akt / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Retina / metabolism
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Retina / pathology
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Signal Transduction
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Vascular Endothelial Growth Factor A / genetics
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Vascular Endothelial Growth Factor A / metabolism*
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Vascular Endothelial Growth Factor Receptor-1 / genetics
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Vascular Endothelial Growth Factor Receptor-1 / metabolism
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Vascular Endothelial Growth Factor Receptor-2 / genetics
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Vascular Endothelial Growth Factor Receptor-2 / metabolism
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beta 2-Glycoprotein I / metabolism*
Substances
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Hypoxia-Inducible Factor 1
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RNA, Messenger
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Vascular Endothelial Growth Factor A
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beta 2-Glycoprotein I
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vascular endothelial growth factor A, mouse
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Kdr protein, mouse
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Vascular Endothelial Growth Factor Receptor-1
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Vascular Endothelial Growth Factor Receptor-2
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Proto-Oncogene Proteins c-akt
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Extracellular Signal-Regulated MAP Kinases
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Oxygen