Figure 4. In vivo patterning and biological effects of VEGF isoforms.

Heparin-binding affinity and proteolytic susceptibility modulate the VEGF patterning in tissues and the subsequent vascular phenotype. A, Angiogenesis in tumor xenografts expressing VEGF₁₂₀ or VEGF₁₁₃ only (left); VEGF₁₆₄ only (middle); VEGF₁₈₈ or the non-cleavable VEGF_{164Δ108–118} only (right). Note differences in spatial distribution with increase in cell-surface associated VEGF (green outlines) in the absence of proteases or in presence of VEGF_188/189 (16, 17, 111). Heavier VEGF isoforms result in networks with greater capillary density, lower caliber, and increased pericyte coverage. B, Hindbrain VEGF distribution and angiogenesis in mice secreting (i) VEGF₁₂₀ only or (ii) wildtype VEGF, which is predominantly VEGF₁₆₄ (15). VEGF localizes closer to the source in wildtype relative to VEGF₁₂₀-secreting hindbrain; note that the two VEGF gradients will intersect if superimposed. C, Postnatal murine retina (14) showed diffuse VEGF distribution (green dots) with a lack of association of VEGF to astrocytes (yellow), plus greater intercellular VEGF in VEGF₁₂₀-only mice (left) compared to wildtype mice or VEGF₁₆₄-only mice (right). Note the enlarged vessels and apparent increase in total VEGF staining in VEGF₁₂₀-secreting retina.