(A) GSEA plot showing negative association with the ‘cell cycle’ gene set in SPHV compared to SPHC. (B) Heatmap representing the expression of genes that are included in the KEGG pathway ‘cell cycle’ and are differentially expressed with a log2(Fold Change)>0.5, FDR < 0.05 when comparing SPHV versus SPHC. Color bar indicates log2(fold change). (C, D) GSEA plots showing, respectively, negative association with ‘pyrimidine metabolism’ and ‘purine metabolism’ gene sets in SPHV compared to SPHC. FDR was accepted when q value < 0.05. (E) Measure of the VEGF-A-induced enzymatic activity of three enzymes involved in de novo nucleotide synthesis in SPHC and SPHV. PPAT, phosphoribosyl pyrophosphate amidotransferase; ATIC, 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase; CAD, carbamoyl-phosphate synthetase 2/aspartate transcarbamylase/dihydroorotase. Data are represented as mean ± SEM of n = 3 experiments. (F) Cell proliferation rate analysis in SPHC and SPHV performed by evaluation of EdU incorporation into the newly synthetized DNA. Representative plots of n = 3 experiments. Data represent the mean percentage of proliferating cells ± SEM of n = 3 experiments. p<0.05 in the comparison between SPHC and SPHV. (G) Sprouting assay performed with ECs pre-treated with the cell replication blocker mitomycin C, and the corresponding quantification of sprout area. Data are represented as mean ± SEM from n = 3 experiments. ***, p<0.001; **, p<0.01; *, p<0.05; ns, not significant.