Microenvironmental VEGF concentration, not total dose, determines a threshold between normal and aberrant angiogenesis
J. Clin. Invest. Clare R. Ozawa, et al. 113:516 doi:10.1172/JCI18420 [Go to this article.]

Figure 4
The microenvironmental level of VEGF produced in muscle determines a threshold between the growth of normal capillaries and hemangiomas. (a) Morphology of vessels at sites of implanted LacZ control cells (Control) and of different VEGF clones at 4 weeks (n = 3–7 per group). Clones 10%, 50%, and 100% produced small-caliber vessels resembling capillaries. Although vessels at sites implanted with 100% clones were uneven in diameter in some regions (arrows), no abnormal bulbous structures were observed in these ears. Aberrant bulbous vascular structures were present in ears implanted with the 180% clone (arrowheads). Large hemangiomas developed in ears implanted with the 325% clone by 4 weeks (H&E stain). (b) The corresponding distributions of vessel diameters at implantation sites are shown below each panel. (c) Morphologies of vessels at sites implanted with the same clones at 2.5–3.5 months after implantation. The capillaries induced by the 10%, 50%, and 100% clones persisted and did not develop any abnormalities, whereas hemangiomas grew in ears implanted with the 180% clone after 2.5 months (H&E stain). The vertical red line and the arrow at the bottom indicate the threshold between the induction of normal capillaries and hemangiomas at a VEGF level between that produced by the 100% and 180% clones. Scale bars: 50 μm (lectin panels, far right in a and c), 1 mm (H&E panel in a), and 0.5 mm (H&E panel in c).