ArticleAmerican journal of physiology. Endocrinology and metabolism2015
Uterine artery dysfunction in pregnant ACE2 knockout mice is associated with placental hypoxia and reduced umbilical blood flow velocity.
Article in American journal of physiology. Endocrinology and metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Guidelines for assessing maternal cardiovascular physiology during pregnancy and postpartum.American journal of physiology. Heart and circulatory physiology · 2024Guideline
- Genetically edited human placental organoids cast new light on the role of ACE2.Cell death & disease · 2025Article
- Sex-specific cardiovascular adaptations to simulated microgravity in Sprague-Dawley rats.NPJ microgravity · 2024Article
- A genetically small fetus impairs placental adaptations near term.Disease models & mechanisms · 2024Article
- Placental ACE2 Expression: A Possible Pathogenetic Mechanism for Infantile Hemangiomas.Dermatopathology (Basel, Switzerland) · 2024Article
- Article
- Review
- miRNA-141-5p Affects the Levels of Neutrophil Elastase in Preeclampsia by Regulating MAPK1.Maternal-fetal medicine (Wolters Kluwer Health, Inc.) · 2022Article
- SARS-CoV-2 modulates virus receptor expression in placenta and can induce trophoblast fusion, inflammation and endothelial permeability.Frontiers in immunology · 2022Article
- ACE2, TMPRSS2, and L-SIGN Expression in Placentae From HIV-Positive Pregnancies Exposed to Antiretroviral Therapy-Implications for SARS-CoV-2 Placental Infection.The Journal of infectious diseases · 2021Article
- ACE2: a key modulator of the renin-angiotensin system and pregnancy.American journal of physiology. Regulatory, integrative and comparative physiology · 2021Article
- Role of ACE2 in pregnancy and potential implications for COVID-19 susceptibility.Clinical science (London, England : 1979) · 2021Review
- Pregnant women with COVID-19: the placental involvement and consequences.Journal of molecular histology · 2021Review
- Coronavirus disease 2019 vaccines in pregnancy.American journal of obstetrics & gynecology MFM · 2021Article
- COVID-19 and developmental origins of health and disease.Early human development · 2021Review
- Opportunities, Challenges and Pitfalls of Using Cannabidiol as an Adjuvant Drug in COVID-19.International journal of molecular sciences · 2021Review
- Letter to the editor: The placenta and COVID-19.Placenta · 2021Article
- SARS-CoV2 and pregnancy: An invisible enemy?American journal of reproductive immunology (New York, N.Y. : 1989) · 2020Review
- ACE2 mouse models: a toolbox for cardiovascular and pulmonary research.Nature communications · 2020Review
- Angiotensin Converting Enzyme 2 (ACE2) in Pregnancy: Preeclampsia and Small for Gestational Age.Frontiers in physiology · 2020Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Angiotensin-converting enzyme 2 (ACE2) knockout is associated with reduced fetal weight at late gestation; however, whether uteroplacental vascular and/or hemodynamic disturbances underlie this growth-restricted phenotype is unknown. Uterine artery reactivity and flow velocities, umbilical flow velocities, trophoblast invasion, and placental hypoxia were determined in ACE2 knockout (KO) and C57Bl/6 wild-type (WT) mice at day 14 of gestation. Although systolic blood pressure was higher in pregnant ACE2 KO vs. WT mice (102.3 ± 5.1 vs. 85.1 ± 1.9 mmHg, n = 5-6), the magnitude of difference was similar to that observed in nonpregnant ACE2 KO vs. WT mice. Maternal urinary protein excretion, serum creatinine, and kidney or heart weights were not different in ACE2 KO vs. WT. Fetal weight and pup-to-placental weight ratio were lower in ACE2 KO vs. WT mice. A higher sensitivity to Ang II [pD2 8.64 ± 0.04 vs. 8.5 ± 0.03 (-log EC50)] and greater maximal contraction to phenylephrine (169.0 ± 9.0 vs. 139.0 ± 7.0% KMAX), were associated with lower immunostaining for Ang II receptor 2 and fibrinoid content of the uterine artery in ACE2 KO mice. Uterine artery flow velocities and trophoblast invasion were similar between study groups. In contrast, umbilical artery peak systolic velocities (60.2 ± 4.5 vs. 75.1 ± 4.5 mm/s) and the resistance index measured using VEVO 2100 ultrasound were lower in the ACE2 KO vs. WT mice. Immunostaining for pimonidazole, a marker of hypoxia, and hypoxia-inducible factor-2α were higher in the trophospongium and placental labyrinth of the ACE2 KO vs. WT. In summary, placental hypoxia and uterine artery dysfunction develop before major growth of the fetus occurs and may explain the fetal growth restricted phenotype.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.