title: Placental growth factor expression is reversed by antivascular endothelial growth factor therapy under hypoxic conditions.
abstract: BACKGROUND
  Clinical trials have revealed that the antivascular 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 (RTPCR). 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).
  
  
  CONCLUSIONS
  The finding that PIGF expression is iatrogenically up-regulated by anti-VEGF therapy provides a consideration to combine it with anti-PIGF therapy.
authors.affiliation: Department of Ophthalmology, the Second Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, 710004, Shaanxi Province, China.
authors.forename: Ai-Yi
authors.initials: AY
authors.lastname: Zhou
authors.forename: Yu-Jing
authors.initials: YJ
authors.lastname: Bai
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.forename: Wen-Zhen
authors.initials: WZ
authors.lastname: Yu
authors.forename: Lv-Zhen
authors.initials: LZ
authors.lastname: Huang
authors.forename: Xiao-Xin
authors.initials: XX
authors.lastname: Li
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D007231:Infant, Newborn; D051379:Mice; D008810:Mice, Inbred C57BL; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000187:drug effects* / Q000378:metabolism; D012160:Retina / Q000378:metabolism / Q000473:pathology; D012178:Retinopathy of Prematurity / Q000378:metabolism / Q000517:prevention & control*; D014471:Umbilical Veins; D015854:Up-Regulation; D042442:Vascular Endothelial Growth Factors / Q000037:antagonists & inhibitors*
chemical_list: C000608036:PGF protein, human; C000608037:Pgf protein, mouse; D011257:Pregnancy Proteins; D042442:Vascular Endothelial Growth Factors; D000072483:Placenta Growth Factor