Comparative evaluation of FGF-2-, VEGF-A-, and VEGF-C-induced angiogenesis, lymphangiogenesis, vascular fenestrations, and permeability

Several endothelial growth factors induce both blood and lymphatic angiogenesis. However, a systematic comparative study of the impact of these factors on vascular morphology and function has been lacking. In this study, we report a quantitative analysis of the structure and macromolecular permeability of FGF- 2 -, VEGF- A -, and VEGF- C - induced blood and lymphatic vessels. Our results show that VEGF- A stimulated formation of disorganized, nascent vasculatures as a result of fusion of blood capillaries into premature plexuses with only a few lymphatic vessels. Ultrastructural analysis revealed that VEGF- A - induced blood vessels contained high numbers of endothelial fenestrations that mediated high permeability to ferritin, whereas the FGF- 2 - induced blood vessels lacked vascular fenestrations and showed only little leakage of ferritin. VEGF- C induced approximately equal amounts of blood and lymphatic capillaries with endothelial fenestrations present only on blood capillaries, mediating a medium level of ferritin leakage into the perivascular space. No endothelial fenestrations were found in FGF- 2 -, VEGF- A -, or VEGF- C - induced lymphatic vessels. These findings highlight the structural and functional differences between blood and lymphatic vessels induced by FGF- 2, VEGF- A, and VEGF- C. Such information is important to consider in development of novel therapeutic strategies using these angiogenic factors.