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Placental growth factor expression is reversed by anti-vascular endothelial growth factor therapy under hypoxic conditions
Ai-Yi Zhou, Yu-Jing Bai, Min Zhao, Wen-Zhen Yu, Lv-Zhen Huang, Xiao-Xin Li
Beijing, China
Author Affiliations: Department of Ophthalmology, the Second Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China (Zhou AY); Key Laboratory of Vision Loss and Restoration, Ministry of Education, Department of Ophthalmology, People's Hospital, Peking University, Beijing, China (Zhou AY, Bai YJ, Zhao M, Yu WZ, Huang LZ, Li XX)
Corresponding Author: Xiao-Xin Li, MD, Key Laboratory of Vision Loss and Restoration, Ministry of Education, Department of Ophthalmology, People's Hospital, Peking University, Xizhimen South Street 11, Xi Cheng District, Beijing 100044, China (Tel: 010-88325413; Fax: 010-88325413; Email: drlixiaoxin@163.com)
doi: 10.1007/s12519-014-0502-0
Background: Clinical trials have revealed that the anti-vascular endothelial growth factor (VEGF) therapies are effective in retinopathy of prematurity (ROP). But the low level of VEGF was necessary as a survival signal in healthy conditions, and endogenous placental growth factor (PIGF) is redundant for development. The purpose of this study was to elucidate the PIGF expression under hypoxia as well as the influence of anti-VEGF therapy on PIGF.
Methods: CoCl2-induced hypoxic human umbilical vein endothelial cells (HUVECs) were used for an in vitro study, and oxygen-induced retinopathy (OIR) mice models were used for an in vivo study. The expression patterns of PIGF under hypoxic conditions and the influence of anti-VEGF therapy on PIGF were evaluated by quantitative reverse transcription-polymerase chain reaction (RT-PCR). The retinal avascular areas and neovascularization (NV) areas of anti-VEGF, anti-PIGF and combination treatments were calculated. Retina PIGF concentration was evaluated by ELISA after treatment. The vasoactive effects of exogenous PIGF on HUVECs were investigated by proliferation and migration studies.
Results: PIGF mRNA expression was reduced by hypoxia in OIR mice, in HUVECs under hypoxia and anti-VEGF treatment. However, PIGF expression was reversed by anti-VEGF therapy in the OIR model and in HUVECs under hypoxia. Exogenous PIGF significantly inhibited HUVECs proliferation and migration under normal conditions, but it stimulated cell proliferation and migration under hypoxia. Anti-PIGF treatment was effective for neovascular tufts in OIR mice (P<0.05).
Conclusion: The finding that PIGF expression is iatrogenically up-regulated by anti-VEGF therapy provides a consideration to combine it with anti-PIGF therapy.
World J Pediatr 2014;10(3):262-270
Key words: human umbilical vein endothelial cells;
oxygen-induced retinopathy;
placental growth factor;
vascular endothelial growth factor
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