To further investigate the relevance of BH4 in the human placental circulation, we investigated the levels of BH4 in placental extracellular vesicles isolated from perfused placentas obtained from women with or without hypertension in pregnancy, a model system previously demonstrated to reflect alterations in key aspects of placental vascular function, including the levels of eNOS.19 We found that BH4 content in placental extracellular vesicles from perfusion of placentas from HTP was significantly lower than those in placental extracellular vesicles from healthy pregnancies (Figure 5F). Here, NOS3 is linked to hypertensive disorder.