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

Circ Res. 2004 Mar 19;94(5):664-70. doi: 10.1161/01.RES.0000118600.91698.BB. Epub 2004 Jan 22.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Capillaries / drug effects
  • Capillaries / ultrastructure*
  • Capillary Permeability / drug effects*
  • Caveolae / physiology
  • Corneal Neovascularization*
  • Drug Implants
  • Endothelium, Vascular / ultrastructure*
  • Ferritins / pharmacokinetics
  • Fibroblast Growth Factor 2 / pharmacology*
  • Humans
  • Image Processing, Computer-Assisted
  • Lymphangiogenesis / drug effects*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Recombinant Fusion Proteins / pharmacology
  • Vascular Endothelial Growth Factor A / pharmacology*
  • Vascular Endothelial Growth Factor C / pharmacology*

Substances

  • Drug Implants
  • Recombinant Fusion Proteins
  • VEGFA protein, human
  • VEGFC protein, human
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor C
  • Fibroblast Growth Factor 2
  • Ferritins