Fig. 9.

Model for STOX1 effects and BH4 therapeutic opportunity to treat preeclampsia. Increased STOX1 expression induces iNOS accumulation and iNOS uncoupling, NO overproduction and subsequently altered pathways: namely nitroso-redox balance and antioxidant defense, bioenergetic metabolism, the Krebs cycle including citrate synthase activity, fumarase activity and the related l-malate, mitochondrial OXPHOS, in the context of altered stability of the hypoxia effector HIF1A. These alterations are potentially related to preeclampsia symptoms. Supplementation of the NOS cofactor BH4 restores iNOS levels and modulates the other altered patways, opening a new therapeutical opportunity to treat preeclampsia symptoms.