Effects of sepiapterin on vascular dysfunction with hypercholesterolemia. Changes in expression of dihydrofolate reductase (DHFR, a BH4 salvage pathway) and GTP cyclohydrolase (GTPCH, de novo synthesis of BH4) with prolonged hypercholesterolemia or lipid lowering. C) Changes in endothelial function after incubation of vessel segments with a precursor for BH4 synthesis (sepiapterin). Note that after 12 months, but not 6 months, HCHOL mice had significant improvement in endothelial function with sepiapterin. For gene expression data, n = 5-13 per group at each time point). For vascular function panels, n = 6-13 for each treatment group at each time point. For gene expression panels, mice were sacrificed at time points denoted on x-axis—offset is provided for clarity and minimization of error bar overlap.