PMID- 17869204
OWN - NLM
STAT- MEDLINE
DCOM- 20071129
LR  - 20071029
IS  - 0002-9394 (Print)
IS  - 0002-9394 (Linking)
VI  - 144
IP  - 5
DP  - 2007 Nov
TI  - Anti-angiogenic effects of ribonucleic acid interference targeting vascular 
      endothelial growth factor and hypoxia-inducible factor-1alpha.
PG  - 761-8
AB  - PURPOSE: To compare the in vitro anti-angiogenic effects of inhibiting vascular 
      endothelial growth factor (VEGF) and hypoxia-inducible factor 1-alpha 
      (HIF-1alpha) using ribonucleic acid (RNA) interference (RNAi). DESIGN: Laboratory 
      investigation. METHODS: VEGF or HIF-1alpha was antagonized in human retinal 
      pigment epithelial (RPE) cells using RNAi, and then cells were cultured under 
      hypoxia. Angiogenic proteins secreted into the media were measured using 
      enzyme-linked immunosorbent assay. Media from hypoxic RPE cells was used to grow 
      human umbilical vein endothelial cells (HUVECs). Capillary tube formation by 
      HUVECs was quantified and compared to assess the effectiveness of angiogenesis. 
      RESULTS: RNAi targeting VEGF caused a significant decrease in VEGF in addition to 
      several other clinically important angiogenic factors, including angiogenin, 
      interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemoattractant protein-1 
      (MCP-1), and tumor growth factor beta(1) (TGF-beta(1)). Although HIF-1alpha RNAi 
      reduced the production of VEGF, angiogenin, and TGF-beta(1), we observed an 
      increase in the levels of several other angiogenic factors like IL-6, IL-8, and 
      MCP-1. RNAi of VEGF and HIF-1alpha was effective in inhibiting angiogenesis, 
      although the effect was more pronounced for VEGF RNAi. CONCLUSIONS: RNAi of VEGF 
      and HIF-1alpha may have therapeutic potential in ischemic retinal diseases like 
      diabetic retinopathy. Targeting VEGF seems to have the advantage of decreasing 
      the production of several clinically important angiogenic factors, thereby 
      effectively inhibiting angiogenesis. Antagonism of HIF-1alpha may lead to the 
      overactivation of alternate transcription factors and their respective gene 
      products, leading to less effective inhibition of angiogenesis.
FAU - Forooghian, Farzin
AU  - Forooghian F
AD  - Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, 
      Toronto, Ontario, Canada. farzin.forooghian@utoronto.ca
FAU - Das, Bikul
AU  - Das B
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070917
PL  - United States
TA  - Am J Ophthalmol
JT  - American journal of ophthalmology
JID - 0370500
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Interleukin-6)
RN  - 0 (Interleukin-8)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
SB  - IM
MH  - Angiogenesis Inhibitors/*pharmacology
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - Endothelium, Vascular/*drug effects/metabolism/pathology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*genetics/metabolism
MH  - Interleukin-6/metabolism
MH  - Interleukin-8/metabolism
MH  - Neovascularization, Pathologic/pathology/*prevention & control
MH  - Pigment Epithelium of Eye/metabolism
MH  - RNA Interference/*drug effects
MH  - RNA, Small Interfering/*pharmacology
MH  - Transfection
MH  - Transforming Growth Factor beta/metabolism
MH  - Umbilical Veins/cytology
MH  - Vascular Endothelial Growth Factor A/*genetics/metabolism
EDAT- 2007/09/18 09:00
MHDA- 2007/12/06 09:00
CRDT- 2007/09/18 09:00
PHST- 2007/05/28 00:00 [received]
PHST- 2007/07/11 00:00 [revised]
PHST- 2007/07/16 00:00 [accepted]
PHST- 2007/09/18 09:00 [pubmed]
PHST- 2007/12/06 09:00 [medline]
PHST- 2007/09/18 09:00 [entrez]
AID - S0002-9394(07)00662-9 [pii]
AID - 10.1016/j.ajo.2007.07.022 [doi]
PST - ppublish
SO  - Am J Ophthalmol. 2007 Nov;144(5):761-8. doi: 10.1016/j.ajo.2007.07.022. Epub 2007 
      Sep 17.