Pathophysiologic mechanisms and molecular targets in preeclampsia

Preeclampsia is a pregnancy-specific multisystem disorder. With a global incidence of 2%-8%, preeclampsia is a major contributor to maternal and neonatal morbidity and mortality. The pathogenesis of preeclampsia is commonly described by a two-stage model. The first stage involves defective placentation in early pregnancy, marked by insufficient extravillous trophoblast invasion, impaired spiral artery remodeling, dysregulated sphingolipid metabolism, and an imbalance in immune tolerance; these anomalies lead to placental ischemia and hypoxia. The second stage consists of systemic maternal responses in the mid-to-late gestation period, including angiogenic imbalance, systemic inflammation, and endothelial dysfunction, which manifest as the clinical symptoms. Recent advances in multi-omics technologies and liquid biopsy have accelerated the discovery of novel biomarkers enabling non-invasive early prediction. Emerging therapeutic strategies target key pathological pathways: low-molecular-weight heparin to restore angiogenic balance and reduce inflammation, complement system inhibitors to counter aberrant activation, and epigenetic modulators to ameliorate endothelial dysfunction. Despite this progress, significant challenges remain, including the heterogeneity of preeclampsia, limited clinical validation of biomarkers and therapeutic targets, and the management of long-term cardiovascular sequelae. Future research should prioritize developing precision prediction models, conducting large-scale clinical trials for targeted therapies, and establishing comprehensive postpartum follow-up systems to improve the prevention, diagnosis, and treatment of preeclampsia.