Abstract
Fibroblast growth factor-1 (FGF-1) is a potent angiogenic factor; its structure lacks a signal peptide for secretion. We previously reported that the overexpression of a secreted version of FGF-1 (sp-FGF-1) in microvascular endothelial cells (ECs) enhances cell migration [Partridge et al. J Cell Biochem 2000; 78(3): 487]. In the current study, we have examined the angiogenic effects of sp-FGF-1 in chicken chorioallantoic membranes (CAMs). Two methods of examining the effects of sp-FGF-1 in CAMs were used: cell-mediated transfection via bovine ECs and direct gene transfection. In the cell-mediated gene transfection, those eggs that were implanted with a gelatin sponge seeded with ECs stably transfected to over-express sp-FGF-1 protein showed a significant increase in angiogenesis inside the sponge when compared to eggs treated with vector control-transfected ECs. In the direct gene transfer, eggs received sp-FGF-1 showed a significant increase in vascularization when compared to eggs received vector alone plasmids. These CAM models are useful both for studying molecular mechanisms of angiogenesis and for developing better gene therapy strategies.
Similar content being viewed by others
References
Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1995; 1(1): 27–31.
Ausprunk DH, Knighton DR, Folkman J. Differentiation of vascular endothelium in the chick chorioallantois: A structural and autoradiographic study. Dev Biol 1974; 38(2): 237–48.
Auerbach R, Auerbach W, Polakowski I. Assays for angiogenesis: A review. Pharmacol Ther 1991; 51(1): 1–11.
Ribatti D, Nico B, Vacca A et al. Chorioallantoic membrane capillary bed: A useful target for studying angiogenesis and antiangiogenesis in vivo. Anat Rec 2001; 264(4): 317–24.
Flamme I, Schulze-Osthoff K, Jacob HJ. Mitogenic activity of chicken chorioallantoic fluid is temporally correlated to vascular growth in the chorioallantoic membrane and related to fibroblast growth factors. Development 1991; 111(3): 683–90.
Schumacher B, Pecher P, von Specht BU, Stegmann T. Induction of neoangiogenesis in ischemic myocardium by human growth factors: First clinical results of a new treatment of coronary heart disease. Circulation 1998; 97(7): 645–50.
Ornitz DM, Itoh N. Fibroblast growth factors. Genome Biol 2001; 2(3): 3005.1–3005.12.
Sellke FW, Ruel M. Vascular growth factors and angiogenesis in cardiac surgery. Ann Thorac Surg 2003; 75(2): S685–90.
Partridge CR, Hawker JR Jr, Forough R. Overexpression of a secretory form of FGF-1 promotes MMP-1–mediated endothelial cell migration. J Cell Biochem 2000; 78(3): 487–99.
Forough R, Xi Z, MacPhee M et al. Differential transforming abilities of non-secreted and secreted forms of human fibroblast growth factor-1. J Biol Chem 1993; 268(4): 2960–8.
Taira M, Yoshida T, Miyagawa K et al. cDNA sequence of human transforming gene hst and identification of the coding sequence required for transforming activity. Proc Natl Acad Sci USA 1987; 84: 2980–4.
Delli Bovi P, Curatola AM, Kern FG et al. An oncogene isolated by transfection of Kaposi’s sarcoma DNA encodes a growth factor that is a member of the FGF family. Cell 1987; 50: 729–37.
Kozak M. Pushing the limits of the scanning mechanism for initiation of translation. Gene 2002; 299(1-2): 1–34.
Schelling ME, Meininger CJ, Hawker JR Jr, Granger HJ. Venular endothelial cells from bovine heart. Am J Physiol 1988; 254: H1211–17.
Diaz-Flores L, Gutierrez R, Varela H. Behavior of postcapillary venule pericytes during postnatal angiogenesis. J Morphol 1992; 213: 33–45.
Thurston G, Baluk P, McDonald DM. Determinants of endothelial cell phenotype in venules. Microcirculation 2000; 7(1): 67–80.
Ribatti D, Nico B, Morbidelli L et al. Cell-mediated delivery of fibroblast growth factor-2 and vascular endothelial growth factor onto the chick chorioallantoic membrane: Endothelial fenestration and angiogenesis. J Vasc Res 2001; 38(4): 389–97.
Messina LM, Podrazik RM, Whitehill TA et al. Adhesion and incorporation of lacZ-transduced endothelial cells into the intact capillary wall in the rat. Proc Natl Acad Sci USA 1992; 89(24): 12018–22.
Edelberg JM, Tang L, Hattori K et al. Young adult bone marrowderived endothelial precursor cells restore aging-impaired cardiac angiogenic function. Circ Res 2002 90(10): E89–E93.
Isner JM, Kalka C, Kawamoto A, Asahara T. Bone marrow as a source of endothelial cells for natural and iatrogenic vascular repair. Ann N Y Acad Sci 2001 953: 75–84.
Madri JA, Kocher O, Merwin JR, et al. The interactions of vascular cells with solid phase (matrix) and soluble factors. J Cardiovasc Pharmacol 1989; 14(Suppl 6): S70–5.
Brindle NP. Growth factors in endothelial regeneration. Cardiovasc Res 1993; 27(7): 1162–72.
Jiang BH, Zheng JZ, Aoki M, Vogt PK. Phosphatidylinositol 3–kinase signaling mediates angiogenesis and expression of vascular endothelial growth factor in endothelial cells. Proc Natl Acad Sci USA 2000; 97(4): 1749–53.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Forough, R., Wang, X., Martinez-Lemus, L.A. et al. Cell-based and direct gene transfer-induced angiogenesis via a secreted chimeric fibroblast growth factor-1 (sp-FGF-1) in the chick chorioallantoic membrane (CAM). Angiogenesis 6, 47–54 (2003). https://doi.org/10.1023/A:1025857229064
Issue Date:
DOI: https://doi.org/10.1023/A:1025857229064