Yan Q, Li Y, Hendrickson A, Sage E H
Department of Vascular Biology, The Hope Heart Institute, Seattle, Washington 98104, USA.
In Vitro Cell Dev Biol Anim. 2001 Jan;37(1):45-9. doi: 10.1290/1071-2690(2001)037<0045:RORCCB>2.0.CO;2.
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.
血管内皮生长因子(VEGF)和碱性成纤维细胞生长因子(bFGF)在视网膜新生血管疾病中起着重要作用。尽管VEGF在视网膜血管生成中的作用已得到充分证实,但bFGF在此过程中的重要性仍需进一步阐明。本研究旨在探讨视网膜毛细血管细胞(内皮细胞和周细胞)在缺氧条件下对bFGF的反应,以及bFGF和VEGF对视网膜内皮细胞增殖和成索形成的潜在协同作用。通过细胞数量和3H-胸腺嘧啶核苷掺入法测定细胞增殖。在I型胶原三维凝胶中评估成索形成。VEGF和bFGF均增加了两种细胞类型的3H-胸腺嘧啶核苷掺入,在缺氧环境中这种作用更为明显。此外,相对于VEGF,bFGF对周细胞增殖的刺激作用更大。然而,在胶原凝胶中,VEGF比bFGF更有效地诱导内皮细胞迁移。在胶原凝胶试验中观察到VEGF和bFGF对细胞侵袭有协同作用。VEGF和bFGF均能增强这些细胞的增殖,尤其是在缺氧条件下。因此,我们认为这两种细胞因子在视网膜血管生成的多个阶段具有协同作用。