Liu Hongyan, Zhou Saijun, Denyer Gareth, Meng Zhenxing, Chen Rui, Lv Lin, Li Chunjun, Yu Demin, Yu Pei
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.
Mol Med Rep. 2015 Feb;11(2):1025-30. doi: 10.3892/mmr.2014.2869. Epub 2014 Nov 5.
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.
β-2-糖蛋白I（β2GPI），也称为载脂蛋白H，是一种由五个同源重复单元组成的磷脂结合血浆蛋白。β2GPI在体外下调血管内皮生长因子（VEGF）信号通路并抑制血管生成。然而，β2GPI降低和β2GPI在视网膜血管生成中的体内作用及效应分子仍未完全明确。在本研究中，使用氧诱导视网膜病变模型来研究β2GPI降低和β2GPI的作用，并监测VEGF、VEGF受体（VEGFR）1、VEGFR-2和缺氧诱导因子1（HIF-1）mRNA的表达以及细胞外信号调节激酶（ERK）和Akt的磷酸化。数据显示，β2GPI和β2GPI降低均抑制视网膜血管生成，并抑制VEGF、VEGFR-1、VEGFR-2、HIF-1、磷酸化-（p-）ERK和p-Akt的表达。β2GPI降低的作用明显强于β2GPI。总之，本研究表明，β2GPI和β2GPI降低可通过下调VEGF及其下游靶点的表达来抑制视网膜血管生成。这表明β-2-糖蛋白I和β2GPI降低在体内可能具有潜在的抗血管生成活性。
