Nutraceutical Targeting of Placental Synthesis of Soluble Fms-Like Tyrosine Kinase- 1 (sFlt-1) as Strategy for Preventing and Controlling Pre-eclampsia

The primary driving force in preeclampsia (PE) appears to be excessive secretion of fms-like tyrosine kinase-1 (sFlt-1), a truncated decoy receptor for vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) that induces systemic endotheliopathy by depriving endothelial cells of the trophic support conferred by VEGF. Factors which boost placental sFlt-1 production in PE include hypoxia - reflecting improper placentation - oxidative stress, and deficient production of hydrogen sulfide (H2S). Nutraceutical measures which may address these issues include taurine and N-acetylcysteine - which may boost placental H2S production; spirulina and phase 2 inducers of heme oxygenase-1 such as lipoic acid - which may down-regulate placental NADPH oxidase activity; and citrulline, high-dose folate, and dietary nitrate - which by supporting placental nitric oxide production may aid proper placentation and hence prevent placental hypoxia. These agents may also help to alleviate the pathogenic impact of sFlt-1 excess. If the utility of such measures can be demonstrated in rodent models of PE, functional foods incorporating these nutraceuticals can be envisioned as aids to a healthful pregnancy. Moreover, rodent studies suggest that such prenatal supplementation may reduce risk for hypertension in adult offspring of the pregnancy. And, since women who develop PE are at markedly higher risk for cardiovascular disorders in their later life, continuing use of such supplementation - promoting effective NO and H2S bioactivity while aiding control of oxidative stress - may be advisable for the mothers.