Abstract | PURPOSE: METHODS: Pellets containing carbamyl-PAF ( cPAF) were implanted in corneas of wild-type or PAF-receptor (PAF-R)-knockout mice, and the progression of angiogenesis was monitored by microscope. In some experiments, mice were treated with a daily intraperitoneal injection of the PAF-R antagonist LAU8080. Migration assays of human umbilical cord vein endothelial cells (HUVECs) and human dermal microvascular endothelial cells (HMVECs) were performed in a Boyden chamber after addition of various concentrations of cPAF or bovine fibroblast growth factor (FGF-2). Cell proliferation was assessed by fluorescence-binding assay in the presence of cPAF or FGF-2 for 8 days. Vascular endothelial growth factor ( VEGF) and FGF-2 expression was studied by RT-PCR and Northern- and Western-blot analyses in cells stimulated with cPAF at different concentrations and for different times. RESULTS: Six days after cPAF pellet implantation, there were new vessels growing from the limbus to the center of the cornea. The PAF-induced neovascularization was significantly reduced in PAF-R-knockout mice and in mice treated with the PAF antagonist. cPAF added to the lower well of the Boyden chamber produced a dose-dependent migration of HUVECs and HMVECs that was inhibited in cells preincubated with LAU8080 or with a VEGF-blocking antibody. In contrast, cPAF did not stimulate proliferation of endothelial cells. cPAF induced VEGF mRNA and protein expression but not FGF-2 expression in HUVECs and HMVECs. CONCLUSIONS:
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Authors | Xiang Ma, Paulo Ottino, Haydee E P Bazan, Nicolas G Bazan |
Journal | Investigative ophthalmology & visual science
(Invest Ophthalmol Vis Sci)
Vol. 45
Issue 9
Pg. 2915-21
(Sep 2004)
ISSN: 0146-0404 [Print] United States |
PMID | 15326102
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Copyright | Copyright Association for Research in Vision and Ophthalmology |
Chemical References |
- Antibodies
- Azepines
- Phospholipid Ethers
- Platelet Activating Factor
- Platelet Membrane Glycoproteins
- RNA, Messenger
- Receptors, G-Protein-Coupled
- Thienopyridines
- Triazoles
- Vascular Endothelial Growth Factor A
- platelet activating factor receptor
- Fibroblast Growth Factor 2
- 1-O-hexadecyl-2-N-methylcarbamylphosphatidylcholine
- BN 50730
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Topics |
- Animals
- Antibodies
(pharmacology)
- Azepines
(pharmacology)
- Cattle
- Cell Division
(drug effects)
- Cell Movement
(drug effects)
- Cells, Cultured
- Corneal Neovascularization
(chemically induced, etiology, prevention & control)
- Dose-Response Relationship, Drug
- Endothelial Cells
(metabolism)
- Fibroblast Growth Factor 2
(metabolism, pharmacology)
- Humans
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Microcirculation
- Phospholipid Ethers
(administration & dosage)
- Platelet Activating Factor
(physiology)
- Platelet Membrane Glycoproteins
(antagonists & inhibitors)
- RNA, Messenger
(metabolism)
- Receptors, G-Protein-Coupled
(antagonists & inhibitors)
- Skin
(blood supply)
- Thienopyridines
- Triazoles
(pharmacology)
- Umbilical Veins
(cytology, physiology)
- Up-Regulation
- Vascular Endothelial Growth Factor A
(genetics, immunology, metabolism)
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