title: Resveratrol Inhibits Hypoxia-Induced Vascular Endothelial Growth Factor Expression and Pathological Neovascularization.
abstract: OBJECTIVE
  To investigate the effects of resveratrol on the expression of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) in human adult retinal pigment epithelial (ARPE-19) cells, and on experimental choroidal neovascularization (CNV) in mice.
  
  
  METHODS
  ARPE-19 cells were treated with different concentrations of resveratrol and then incubated under hypoxic conditions with subsequent evaluation of cell viability, expression of HIF-1α, and expression of VEGF. The effects of resveratrol on the synthesis and degradation of hypoxia-induced HIF-1α were evaluated using inhibitors of the PI3K/Akt/mTOR and the ubiquitin proteasome pathways. In animal studies, CNV lesions were induced in C57BL/6 mice by laser photocoagulation. After 7 days of oral administration of resveratrol or vehicle, which began one day after CNV induction, image analysis was used to measure CNV areas on choroidal flat mounts stained with isolectin IB4.
  
  
  RESULTS
  In ARPE-19 cells, resveratrol significantly inhibited HIF-1α and VEGF in a dose-dependent manner, by blocking the PI3K/Akt/mTOR signaling pathway and by promoting proteasomal HIF-1α degradation. In mice experiments, orally administered resveratrol significantly inhibited CNV growth in a dose-dependent manner.
  
  
  CONCLUSIONS
  Resveratrol may have therapeutic value in the management of diseases involving pathological neovascularization.
authors.affiliation: The Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Severance Hospital, Seoul, Korea.
authors.forename: Christopher Seungkyu
authors.initials: CS
authors.lastname: Lee
authors.affiliation: Department of Biotechnology, College of Life Science, CHA University, Seongnam, Korea.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Choi
authors.affiliation: The Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Severance Hospital, Seoul, Korea.
authors.forename: Sung Chul
authors.initials: SC
authors.lastname: Lee
authors.affiliation: The Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Severance Hospital, Seoul, Korea.
authors.forename: Hyoung Jun
authors.initials: HJ
authors.lastname: Koh
authors.affiliation: Myung-gok Eye Research Institute, Konyang University College of Medicine, Kim's Eye Hospital, Seoul, Korea.
authors.forename: Joon Haeng
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Biotechnology, College of Life Science, CHA University, Seongnam, Korea. jhchung@cha.ac.kr.
authors.forename: Ji Hyung
authors.initials: JH
authors.lastname: Chung
mesh_terms: D000328:Adult; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D020256:Choroidal Neovascularization / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D046988:Proteasome Endopeptidase Complex; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000502:physiology*; D000077185:Resveratrol; D055213:Retinal Pigment Epithelium / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction; D013267:Stilbenes / Q000008:administration & dosage / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D025801:Ubiquitin; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects* / Q000378:metabolism
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D046988:Proteasome Endopeptidase Complex; D051057:Proto-Oncogene Proteins c-akt; D000077185:Resveratrol; D013267:Stilbenes; D058570:TOR Serine-Threonine Kinases; D025801:Ubiquitin; D042461:Vascular Endothelial Growth Factor A; C546842:MTOR protein, human; C494918:AKT1 protein, human
keywords: Choroidal neovascularization; hypoxia-inducible factor-1; resveratrol; retinal pigment epithelium; vascular endothelial growth factor