GCH1 and hyperhomocysteinemia: Given that both GTPCH1 and DHFR genes harbor the cognate cis-elements within the 5′-flanking regions, we speculate that STA may activate Nrf2 to transcriptionally up-regulate the gene expression of GTPCH1 and DHFR, which are responsible for the de novo biosynthesis and salvage pathways of BH4; such a coordinated gene induction result in increased BH4 and NO bioavailability, thus protecting endothelial-dependent vascular function against such metabolic risk factor as homocysteinemia, saturated free fatty acids and Ang II (Fig. 7).