ArticleThe Journal of physiology2016
Human placental renin-angiotensin system in normotensive and pre-eclamptic pregnancies at high altitude and after acute hypoxia-reoxygenation insult.
Article in The Journal of physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Analysis of the evolution of placental oxidative stress research from a bibliometric perspective.Frontiers in pharmacology · 2024Pooled it
- The uteroplacental circulation at high altitude: adaptation and maladaptation.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- Integrative transcriptomic analysis reveals alternative splicing complexity and transcriptomic diversity in porcine placentas across altitudes.DNA research : an international journal for rapid publication of reports on genes and genomes · 2025Article
- HIF-1α knockdown attenuates phenotypic transformation and oxidative stress induced by high salt in human aortic vascular smooth muscle cells.Scientific reports · 2024Article
- ATP6AP2, a regulator of LRP6/β-catenin protein trafficking, promotes Wnt/β-catenin signaling and bone formation in a cell type dependent manner.Bone research · 2024Article
- Article
- Primary Human Trophoblasts Mimic the Preeclampsia Phenotype after Acute Hypoxia-Reoxygenation Insult.Cells · 2022Article
- Role of the Uteroplacental Renin-Angiotensin System in Placental Development and Function, and Its Implication in the Preeclampsia Pathogenesis.Biomedicines · 2021Review
- Fetal growth, high altitude, and evolutionary adaptation: a new perspective.American journal of physiology. Regulatory, integrative and comparative physiology · 2021Article
- Pregnancy-related acute kidney injury at high altitude: a retrospective observational study in a single center.BMC nephrology · 2021Observational
- Maternal Exposure to Ambient Air Pollution and Risk of Preeclampsia: A Population-Based Cohort Study in Scania, Sweden.International journal of environmental research and public health · 2020Article
- The Differential Expression of ERAP1/ERAP2 and Immune Cell Activation in Pre-eclampsia.Frontiers in immunology · 2020Article
- The (pro)renin receptor in health and disease.Nature reviews. Nephrology · 2019Review
- Placental CX3CL1 is Deregulated by Angiotensin II and Contributes to a Pro-Inflammatory Trophoblast-Monocyte Interaction.International journal of molecular sciences · 2019Article
- Gestational Hypoxia and Programing of Lung Metabolism.Frontiers in physiology · 2019Review
- Gestational Hypoxia and Developmental Plasticity.Physiological reviews · 2018Review
- Consensus strategy in genes prioritization and combined bioinformatics analysis for preeclampsia pathogenesis.BMC medical genomics · 2017Article
- Infantile Hemangiomas: An Updated Review on Risk Factors, Pathogenesis, and Treatment.Birth defects research · 2017Review
- Preeclampsia and the brain: neural control of cardiovascular changes during pregnancy and neurological outcomes of preeclampsia.Clinical science (London, England : 1979) · 2016Review
- Hypoxia, fetal and neonatal physiology: 100 years on from Sir Joseph Barcroft.The Journal of physiology · 2016Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
A functioning placental renin-angiotensin system (RAS) appears necessary for uncomplicated pregnancy and is present during placentation, which occurs under low oxygen tensions. Placental RAS is increased in pre-eclampsia (PE), characterised by placental dysfunction and elevated oxidative stress. We investigated the effect of high altitude hypoxia on the RAS and hypoxia-inducible factors (HIFs) by measuring mRNA and protein expression in term placentae from normotensive (NT) and PE women who delivered at sea level or above 3100 m, using an explant model of hypoxia-reoxygenation to assess the impact of acute oxidative stress on the RAS and HIFs. Protein levels of prorenin (P = 0.049), prorenin receptor (PRR; P = 0.0004), and angiotensin type 1 receptor (AT1R, P = 0.006) and type 2 receptor (AT2R, P = 0.002) were all significantly higher in placentae from NT women at altitude, despite mRNA expression being unaffected. However, mRNA expression of all RAS components was significantly lower in PE at altitude than at sea level, yet PRR, angiotensinogen (AGT) and AT1R proteins were all increased. The increase in transcript and protein expression of all the HIFs and NADPH oxidase 4 seen in PE compared to NT at sea level was blunted at high altitude. Experimentally induced oxidative stress stimulated AGT mRNA (P = 0.04) and protein (P = 0.025). AT1R (r = 0.77, P < 0.001) and AT2R (r = 0.81, P < 0.001) mRNA both significantly correlated with HIF-1β, whilst AT2R also correlated with HIF-1α (r = 0.512, P < 0.013). Our observations suggest that the placental RAS is responsive to changes in tissue oxygenation: this could be important in the interplay between reactive oxygen species as cell-signalling molecules for angiogenesis and hence placental development and function.
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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 OpenQuestion graph.