Alpha-1 microglobulin as a potential therapeutic candidate for treatment of hypertension and oxidative stress in the STOX1 preeclampsia mouse model

Preeclampsia is a human placental disorder affecting 2-8% of pregnancies worldwide annually, with hypertension and proteinuria appearing after 20 weeks of gestation. The underlying cause is believed to be incomplete trophoblast invasion of the maternal spiral arteries during placentation in the first trimester, resulting in oxidative and nitrative stress as well as maternal inflammation and organ alterations. In the Storkhead box 1 (STOX1) preeclampsia mouse model, pregnant females develop severe and early onset manifestations as seen in human preeclampsia e.g. gestational hypertension, proteinuria, and organ alterations. Here we aimed to evaluate the therapeutic potential of human recombinant alpha-1 microglobulin (rA1M) to alleviate the manifestations observed. Human rA1M significantly reduced the hypertension during gestation and significantly reduced the level of hypoxia and nitrative stress in the placenta. In addition, rA1M treatment reduced cellular damage in both placenta and kidneys, thereby protecting the tissue and improving their function. This study confirms that rA1M has the potential as a therapeutic drug in preeclampsia, and likely also in other pathological conditions associated with oxidative stress, by preserving normal organ function.