Regulation of retinal capillary cells by basic fibroblast growth factor, vascular endothelial growth factor, and hypoxia.
Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) feature prominently in retinal neovascular diseases. Although the role of VEGF in retinal angiogenesis is well established, the importance of bFGF in this process requires further clarification. This study was undertaken to investigate the responses of retinal capillary cells (endothelial cells and pericytes) to bFGF under hypoxic conditions, as well as the potentially synergistic effects of bFGF and VEGF on the proliferation and cord formation of retinal endothelial cells. Cell proliferation was determined by cell number and by 3H-thymidine incorporation. Cord formation was assessed in three-dimensional gels of collagen type I. VEGF and bFGF increased 3H-thymidine incorporation by both cell types, an effect that was more pronounced in a hypoxic environment. Moreover, the proliferation of pericytes was stimulated to a greater extent by bFGF relative to VEGF. Endothelial migration in collagen gels, however, was induced more effectively by VEGF than by bFGF. A synergistic effect of VEGF and bFGF on cell invasion was observed in the collagen gel assay. VEGF and bFGF each augment proliferation of these cells, especially under hypoxia. We thus propose that these two cytokines have a synergistic effect at several stages of angiogenesis in the retina.
Yan
Q
Q
Department of Vascular Biology, The Hope Heart Institute, Seattle, Washington 98104, USA.
Li
Y
Y
Hendrickson
A
A
Sage
E H
EH
D000818:Animals; D002196:Capillaries / Q000166:cytology; D002417:Cattle; D002454:Cell Differentiation; D002455:Cell Division; D015687:Cell Hypoxia; D002478:Cells, Cultured; D016228:Endothelial Growth Factors / Q000494:pharmacology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology / Q000502:physiology*; D008222:Lymphokines / Q000494:pharmacology / Q000502:physiology*; D018919:Neovascularization, Physiologic; D020286:Pericytes / Q000502:physiology; D012160:Retina / Q000166:cytology*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2