Vascular Mechanisms in Hypertensive Pregnancy

Hypertensive disorders of pregnancy, most notably preeclampsia, arise from impaired adaptation of the maternal vasculature to gestation. In normal pregnancy, spiral arteries undergo physiological remodelling that transforms high‐resistance vessels into low‐resistance conduits, ensuring adequate uteroplacental blood flow. In hypertensive pregnancies this process is incomplete, leading to placental ischaemia, oxidative stress and release of antiangiogenic factors into the maternal circulation. Endothelial dysfunction ensues, characterised by reduced nitric oxide bioavailability, diminished prostacyclin production and heightened sensitivity to vasoconstrictors. Concomitant alterations in matrix metalloproteinase activity and extracellular matrix composition increase vascular stiffness and peripheral resistance. Emerging evidence also implicates dysregulation of ubiquitin ligase pathways, notably cullin‐3 complexes, in promoting vasoconstriction and sodium retention. These vascular maladaptations not only contribute to maternal hypertension and end‐organ injury, but also to fetal growth restriction and long‐term cardiovascular risk for mother and offspring. Better understanding of these mechanisms underpins the development of targeted therapies, including modulation of angiogenic balance, nitrate supplementation and interventions directed at oxidative stress.

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Vascular Mechanisms in Hypertensive Pregnancy publication trend

The graph below shows the total number of articles in vascular mechanisms in hypertensive pregnancy across all publications each year (not limited to Nature Index journals).

Technical terms

Spiral artery remodelling: The physiological transformation of uterine spiral arteries into low-resistance vessels to support placental perfusion.

Endothelial dysfunction: A state in which the vascular endothelium loses its normal balance of vasodilation and vasoconstriction mediators, leading to increased vascular tone and inflammation.

Nitric oxide synthase (NOS): Enzymes that produce nitric oxide; endothelial NOS (eNOS) supports vasodilation, whereas inducible NOS (iNOS) is upregulated in inflammatory states.

Matrix metalloproteinases (MMPs): A family of zinc-dependent proteases that degrade extracellular matrix components, crucial for vascular and placental remodelling.

Antiangiogenic factors: Circulating molecules such as soluble fms-like tyrosine kinase-1 that bind and neutralise pro-angiogenic growth factors, disrupting endothelial function.

Ubiquitin ligase cullin-3 complex: A multiprotein enzyme assembly that tags specific substrates for degradation, regulating vascular tone and sodium transport in hypertensive disorders.

References

1. Impaired Endothelium-Dependent Vasodilation and Increased Levels of Soluble Fms-like Tyrosine Kinase-1 Induced by Reduced Uterine Perfusion Pressure in Pregnant Rats: Evidence of Protective Effects with Sodium Nitrite Treatment in Preeclampsia. International Journal of Molecular Sciences (2024).
2. Role of Gelatinases MMP-2 and MMP-9 in Healthy and Complicated Pregnancy and Their Future Potential as Preeclampsia Biomarkers. Diagnostics (2021).
3. Downregulation of Cullin 3 Ligase Signaling Pathways Contributes to Hypertension in Preeclampsia. Frontiers in Cardiovascular Medicine (2021).