Regulation of expression of vasoactive genes by Dll4-Fc and VEGF-A. (A-C) Morphologic changes in the retinal vasculature 24 hours after treatment with 4 μg of Dll4-Fc (B) or 1 μg of VEGF-A (C) compared with 4 μg of Fc (A). (D) Venn diagram showing similarity and difference between Dll4-Fc and VEGF-A significantly regulated genes. (E) Regulation of Dll4/Notch and VEGF-A target genes and vasoactive proteins by Dll4-Fc and VEGF-A. The vasodilators (red) were up-regulated and vasoconstrictors (blue) are down-regulated by Dll4-Fc. Table (left) and corresponding heat map (right) showing changes in the retinal gene expression within 24 hours of treatment. Gene symbols are as follows: Hes indicates hairy and enhancer of split; Hey, hairy/enhancer-of-split related with YRPW motif; Esm1, endothelial cell-specific molecule 1; Ang2, angiopoietin 2; Nts, neurotensin; Adm, adrenomedullin; Nostrin, nostrin; Ace2, angiotensin I-converting enzyme 2; Agt, angiotensinogen; Edn2, endothelin 2; and Ednra, endothelin receptor type A. (F-K) Reverse-transcribed polymerase chain reaction (TaqMan) analysis of Notch target genes (C-D), vasodilators (E-F), and vasoconstrictors (G-H).