Pathophysiology of Preeclampsia and Related Hypertensive Disorders

Preeclampsia and related hypertensive disorders of pregnancy arise from maladaptive interactions between the developing placenta and maternal vasculature. In a normal pregnancy, extravillous trophoblasts invade maternal spiral arteries to increase uteroplacental blood flow. Failure of spiral artery remodelling leads to placental ischaemia, oxidative stress and release of anti-angiogenic factors into the maternal circulation. A key mediator is soluble fms-like tyrosine kinase-1 (sFlt-1), which binds and neutralises vascular growth factors, provoking systemic endothelial dysfunction, hypertension and end-organ injury. Concurrently, aberrant immune activation drives inflammatory pathways, including pyroptotic cell death in the placenta, further exacerbating vascular damage. Subtypes such as early-onset and late-onset preeclampsia exhibit distinct timing and severity, reflecting differences in placental development, maternal endothelial resilience and genetic or environmental predispositions. Emerging evidence also implicates metabolic and microbial signals, linking maternal gut dysbiosis to vascular and inflammatory alterations. Ongoing research seeks to identify predictive biomarkers, refine subtype classification and develop targeted interventions that restore angiogenic balance, mitigate oxidative damage and improve outcomes for mother and child.

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Pathophysiology of Preeclampsia and Related Hypertensive Disorders publication trend

The graph below shows the total number of articles in pathophysiology of preeclampsia and related hypertensive disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Trophoblast: Specialized placental cells that invade the maternal uterus to establish blood flow.

Spiral artery remodelling: The transformation of maternal uterine arteries by trophoblasts to increase placental perfusion.

sFlt-1: Soluble fms-like tyrosine kinase-1, an anti-angiogenic protein that binds vascular growth factors and impairs endothelial function.

Oxidative stress: Cellular damage caused by an imbalance between reactive oxygen species and antioxidant defences.

Angiogenesis: The formation of new blood vessels from pre-existing vasculature, essential for placental development.

Pyroptosis: A form of inflammatory cell death that releases cytokines and amplifies the immune response.

Trimethylamine N-oxide (TMAO): A gut microbiota-derived metabolite implicated in vascular inflammation and hypertension.

References

1. RGS2 promotes estradiol biosynthesis by trophoblasts during human pregnancy. Experimental & Molecular Medicine (2023).
2. Two decades of advances in preeclampsia research: molecular mechanisms and translational studies. Journal of Clinical Investigation (2024).
3. Gut microbiota-derived trimethylamine N-Oxide: a novel target for the treatment of preeclampsia. Gut Microbes (2024).
4. Pyroptosis is a critical inflammatory pathway in the placenta from early onset preeclampsia and in human trophoblasts exposed to hypoxia and endoplasmic reticulum stressors. Cell Death & Disease (2019).