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 2
A reduction in the total amount of VEGF does not eliminate abnormal vascular growth. Delivery of a smaller proportion of VEGF myoblasts (less total VEGF) failed to prevent aberrant vascular growth at 28 days. (a) Lectin staining of the vasculature revealed focal growth of morphologically abnormal, bulbous vascular structures in ears implanted with a mixture consisting of 7–100% VEGF myoblasts, with the remainder being control myoblasts. Vessels in control ears implanted with 100% LacZ myoblasts had a normal appearance. Myoblasts were stained for LacZ expression using the X-gal reaction (blue). (b) Implantation of increasing proportions of VEGF myoblasts resulted in larger areas (mm²) of VEGF-induced vascular growth. Tracings of areas of vascular growth shown are from one representative sample per group; n values and average area for each group are indicated. (c) Vessel diameter distribution measured at implantation sites of the control and VEGF myoblast dilutions shown in a. Implantation of different dilutions of the heterogeneous VEGF myoblast population invariably led to growth of vessels with similarly large and heterogeneous diameters. Min, minimum; Max, maximum. Scale bars: 50 μm (a) and 300 μm (b).