ArticleProceedings of the National Academy of Sciences of the United States of America2016
Pravastatin ameliorates placental vascular defects, fetal growth, and cardiac function in a model of glucocorticoid excess.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- The effect of antenatal corticosteroid use on offspring cardiovascular function: A systematic review.BJOG : an international journal of obstetrics and gynaecology · 2023Pooled it
- Feto-placental blood vessel development.Development (Cambridge, England) · 2025Review
- A Reduction in Antenatal Steroid Dose Was Associated with Reduced Cardiac Dysfunction in a Sheep Model of Pregnancy.Reproductive sciences (Thousand Oaks, Calif.) · 2023Article
- The Effects of Prenatal Pravastatin Treatment in the Rabbit Fetal Growth Restriction Model.Biomedicines · 2023Article
- Combined Statin and Glucocorticoid Therapy for the Safer Treatment of Preterm Birth.Hypertension (Dallas, Tex. : 1979) · 2023Article
- Life Course Impact of Glucocorticoids During Pregnancy on Muscle Development and Function.Frontiers in animal science · 2021Article
- Analysis of Placental Arteriovenous Formation Reveals New Insights Into Embryos With Congenital Heart Defects.Frontiers in genetics · 2021Article
- Antenatal dexamethasone treatment transiently alters diastolic function in the mouse fetal heart.The Journal of endocrinology · 2019Article
- The Placental Transcriptome in Late Gestational Hypoxia Resulting in Murine Intrauterine Growth Restriction Parallels Increased Risk of Adult Cardiometabolic Disease.Scientific reports · 2019Article
- Glucocorticoids, antenatal corticosteroid therapy and fetal heart maturation.Journal of molecular endocrinology · 2018Review
- Recent Advances in Placenta-Heart Interactions.Frontiers in physiology · 2018Review
- Treating the dysfunctional placenta.The Journal of endocrinology · 2017Review
- Antenatal endogenous and exogenous glucocorticoids and their impact on immune ontogeny and long-term immunity.Seminars in immunopathology · 2016Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fetoplacental glucocorticoid overexposure is a significant mechanism underlying fetal growth restriction and the programming of adverse health outcomes in the adult. Placental glucocorticoid inactivation by 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) plays a key role. We previously discovered that Hsd11b2(-/-) mice, lacking 11β-HSD2, show marked underdevelopment of the placental vasculature. We now explore the consequences for fetal cardiovascular development and whether this is reversible. We studied Hsd11b2(+/+), Hsd11b2(+/-), and Hsd11b2(-/-) littermates from heterozygous (Hsd11b(+/-)) matings at embryonic day (E)14.5 and E17.5, where all three genotypes were present to control for maternal effects. Using high-resolution ultrasound, we found that umbilical vein blood velocity in Hsd11b2(-/-) fetuses did not undergo the normal gestational increase seen in Hsd11b2(+/+) littermates. Similarly, the resistance index in the umbilical artery did not show the normal gestational decline. Surprisingly, given that 11β-HSD2 absence is predicted to initiate early maturation, the E/A wave ratio was reduced at E17.5 in Hsd11b2(-/-) fetuses, suggesting impaired cardiac function. Pravastatin administration from E6.5, which increases placental vascular endothelial growth factor A and, thus, vascularization, increased placental fetal capillary volume, ameliorated the aberrant umbilical cord velocity, normalized fetal weight, and improved the cardiac function of Hsd11b2(-/-) fetuses. This improved cardiac function occurred despite persisting indications of increased glucocorticoid exposure in the Hsd11b2(-/-) fetal heart. Thus, the pravastatin-induced enhancement of fetal capillaries within the placenta and the resultant hemodynamic changes correspond with restored fetal cardiac function. Statins may represent a useful therapeutic approach to intrauterine growth retardation due to placental vascular hypofunction.
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