We recently reported that selective deficiency in endothelial cell BH4 biosynthesis, in an endothelial cell-specific Gch1 knockout (Gch1fl/flTie2cre) mouse, is sufficient to cause eNOS uncoupling, endothelial dysfunction, and mild hypertension, in healthy animals.8,9 However, it is unclear to what extent there is a specific requirement for endothelial cell BH4 in modulating susceptibility to structural vascular disease and whether selective endothelial cell BH4 deficiency is sufficient to drive pathological changes in the vascular wall. Here, GCH1 is linked to endothelial dysfunction.