New research reveals biological mechanism behind preeclampsia, offering path toward potential cure

New research published in the journal Circulation reveals that dysregulation of the VGLL3 gene in placental trophoblast cells may be the root cause of preeclampsia, a condition killing 70,000 women annually. In mouse models, targeting this gene successfully reversed preeclampsia symptoms. Meanwhile, a massive Norwegian study of 1 million women published in the European Heart Journal shows that pregnancy complications double premature cardiovascular death risks, with specific pregnancy sequences altering risk levels up to 3.3-fold.

VGLL3 gene discovery

• ▪In mouse models, the overexpression of the VGLL3 gene caused high blood pressure, while inhibiting or deleting the gene resulted in normal, healthy pregnancies.
• ▪Researchers published a study in the journal Circulation suggesting that dysregulation of the VGLL3 gene in the placenta may be the root cause of preeclampsia.
• ▪The VGLL3 gene acts as a transcription cofactor that regulates biological processes including cell growth, immune regulation, metabolism, and hormonal signaling.

Preeclampsia diagnostic challenges

• ▪Current medical guidelines state that preeclampsia occurs after 20 weeks of gestation and requires multiple blood pressure readings above 140/90.
• ▪Preeclampsia symptoms can include high blood pressure, headaches, shortness of breath, nausea, and confusion, though symptoms often go undetected until severe complications develop.

Placental trophoblast biology

• ▪Preeclampsia and its symptoms stem from the placenta, specifically involving specialized cells called trophoblasts that exist only during pregnancy.
• ▪Trophoblast cells produce a protein called sFLT-1, a key biomarker involved in vascular dysregulation that is used in FDA-approved blood tests to predict preeclampsia risk.

Cardiovascular mortality risk

• ▪The Norwegian study analyzed data from approximately 1 million women between 1967 and 2020, examining complications including preeclampsia, gestational hypertension, and preterm delivery.
• ▪A Norwegian nationwide study published in the European Heart Journal found that women who experience pregnancy complications face roughly twice the risk of premature cardiovascular death.

Pregnancy history patterns

• ▪Women whose first pregnancy was complicated and who had no subsequent pregnancies faced a 3.3-fold higher risk of premature cardiovascular death compared to women with multiple uncomplicated pregnancies.
• ▪Women who experienced a pregnancy complication in their first pregnancy and another complication in a later pregnancy faced a 2.4-fold higher risk of premature cardiovascular death.