MinireviewA new approach regarding the treatment of preeclampsia and preterm labor

Both preeclampsia and preterm delivery are important complications in pregnancy and are leading causes for maternal and perinatal morbidity and mortality. The underlying molecular mechanisms of both diseases remain unknown, thus treatments (beta2-stimulants and magnesium sulfate) are essentially symptomatic. Both molecules have molecular weights less than 5-8 kDa and cross the placental barrier thus exerting their effects on the fetus. In addition, the fetus produces peptide hormones that are highly vasoactive and uterotonic and increase in response to maternal stress and with continued development. Fetal peptides are also small molecules that inevitably leak across into the maternal circulation. Aminopeptidases such as placental leucine aminopeptidase (P-LAP) and aminopeptidase A (APA) are large molecules that do not cross the placental barrier. We have shown that APA acts as an antihypertensive agent in the pregnant spontaneously hypertensive rat by degrading vasoactive peptides and as a result returns the animal to a normotensive state. We have also noted that P-LAP acts as an anti-uterotonic agent by degrading uterotonic peptides, and as a result prolongs gestation in the pregnant mouse. Thus, P-LAP and APA represent promising agents for the treatment of preeclampsia and preterm labor by degrading bioactive hormones derived from the feto-placental circulation.