EGF is known to promote the formation of new blood vessels by inducing endothelial cell (EC) proliferation and migration. Brefeldin A (BFA)-inhibited guanine nucleotide-exchange proteins (BIGs) 1 and 2 accelerate the activation of ADP-ribosylation factor (Arf) 1, which regulates vesicular transport between the Golgi and plasma membrane by replacing bound GDP with GTP. While previous studies have suggested that treatment with BFA can inhibit VEGF secretion by interfering with Arf1 activation, the exact role of BIG1 and BIG2 in VEGF trafficking, expression, EC migration and proliferation, and vascular development remains unclear.

Our study found that angioblast migration and intersegmental vessel sprouting were impaired when the BIG2 homolog, Arf guanine nucleotide exchange factor (arfgef) 2, was knocked down in zebrafish with the endothelial expression of green fluorescent protein (GFP). Moreover, the depletion of arfgef2 by CRISPR/Cas9 also resulted in vascular development defects in zebrafish embryos. These findings suggest that BIG1 and BIG2 play a crucial role in endothelial cell angiogenesis. (Chen et al., 2020; Han et al., 2018; Li et al., 2022; Lu et al., 2019; Rothschild et al., 2020)