NOS3 and cardiovascular disorder: Targeting BH4 is a rational therapeutic strategy in cardiovascular disease, but future studies should be directed toward interventions that can favorably alter the endogenous BH4/BH2 ratio and augment BH4 binding to eNOS in human vascular endothelium via a selective increase in absolute BH4 levels, prevention of BH4 oxidation, or increased BH4 recycling.