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Author Spotlight: Modeling an Aspect of Preeclampsia in Female Mice Using Hypoxic Human Placenta-Derived Small Extracellular Vesicles
Published on: January 26, 2024
Emerging drugs for preeclampsia--the endothelium as a target
Jennifer M Sasser1, Sydney R Murphy1, Joey P Granger2
1a 1 University of Mississippi Medical Center, Department of Pharmacology and Toxicology , 2500 North State Street, Jackson, MS 39216, USA +1 601 984 1629 ; +1 601 984 1637 ; jsasser@umc.edu.
Insights
Preeclampsia, a pregnancy complication causing hypertension and proteinuria, impacts 3-8% of pregnancies. Therapies targeting endothelial dysfunction, like PDE-5 inhibitors and endothelin receptor blockers, show promise for managing symptoms and improving outcomes.
Area of Science:
- Obstetrics and Gynecology
- Cardiovascular Research
- Pharmacology
Background:
- Preeclampsia affects 3-8% of pregnancies, leading to significant maternal and perinatal morbidity and mortality.
- Characterized by systemic endothelial dysfunction, preeclampsia lacks sufficient therapeutic options.
- Understanding pathological mechanisms is advancing, yet clinical management remains limited.
Discussion:
- Endothelial dysfunction is central to preeclampsia's maternal syndrome.
- Agents improving endothelial function may alleviate symptoms and improve neonatal outcomes.
- Focus on PDE-5 inhibition and endothelin type A receptor antagonism for vasodilation and reduced vascular contraction.
Key Insights:
- PDE-5 inhibition preserves nitric oxide-cGMP signaling, promoting vasodilation.
- Endothelin type A receptor inhibition reduces vascular contraction.
- Both therapies are approved for other indications, suggesting potential repurposing for preeclampsia.
Outlook:
- Investigating PDE-5 inhibitors and endothelin receptor blockers could offer new preeclampsia management strategies.
- These therapies may delay preterm delivery and enhance neonatal outcomes.
- Further research is warranted to establish efficacy and safety in preeclampsia management.
Abstract:
Preeclampsia, the development of new onset hypertension and proteinuria during pregnancy, affects ∼ 3 - 8% of all pregnancies and is a leading cause of maternal and perinatal morbidity and mortality. Despite the potentially devastating effects of this disease on the mother and the baby and the recent advances in understanding some of the pathological mechanisms responsible for the progression of preeclampsia, there are still few therapies available to manage the disease. The maternal syndrome of preeclampsia is characterized by systemic endothelial dysfunction; therefore, agents that improve endothelial function may hold promise to alleviate the symptoms of preeclampsia, delay the necessity for preterm delivery and improve neonatal outcomes. This brief review will focus on two therapies that are already approved for use in the US for other indications: PDE-5 inhibition to preserve nitric oxide - cGMP signaling to promote vasodilation and inhibition of the endothelin type A receptor to reduce vascular contraction.
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