ArticleClinical science (London, England : 1979)2020
Hypoxia-induced small extracellular vesicle proteins regulate proinflammatory cytokines and systemic blood pressure in pregnant rats.
Article in Clinical science (London, England : 1979), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 36 citations in OpenAlex.
- Placental Small Extracellular Vesicles Undetected in Cerebrospinal Fluid of Preeclamptic and Eclamptic Women.Biomolecules · 2026Article
- Flow Cytometric Detection of Biomarker Changes in CFDA-SE-Labelled Plasma Extracellular Vesicles Using a Rodent Pregnancy Model of Prenatal Diagnostics.Journal of extracellular biology · 2026Article
- The Role of Exosomes in Offspring Metabolic Programming in Gestational Diabetes: Mechanisms and Potential Applications.International journal of biological sciences · 2026Review
- Gut-placenta axis: gut microbiota metabolites may play a role in regulating maternal-fetal immune tolerance and the pathogenesis of adverse pregnancy outcomes.Frontiers in immunology · 2026Review
- Regulatory roles of extracellular vesicles in pregnancy complications.Journal of advanced research · 2025Review
- The molecular pathogenesis of placenta accreta spectrum disorder and its clinical applications.Archives of gynecology and obstetrics · 2025Review
- Hypoxia in extravillous trophoblasts links maternal obesity and offspring neurobehavior.iScience · 2025Article
- Therapeutic potential of extracellular vesicles for treating human pregnancy disorders.Extracellular vesicles and circulating nucleic acids · 2025Review
- Placenta Extracellular Vesicles: Messengers Connecting Maternal and Fetal Systems.Biomolecules · 2024Review
- Extracellular vesicles as markers and mediators of pregnancy complications: gestational diabetes, pre-eclampsia, preterm birth and fetal growth restriction.The Journal of physiology · 2023Review
- Cell culture-derived extracellular vesicles: Considerations for reporting cell culturing parameters.Journal of extracellular biology · 2023Article
- Small extracellular vesicles-transported lncRNA TDRKH-AS1 derived from AOPPs-treated trophoblasts initiates endothelial cells pyroptosis through PDIA4/DDIT4 axis in preeclampsia.Journal of translational medicine · 2023Article
- Associations of maternal and placental extracellular vesicle miRNA with preeclampsia.Frontiers in cell and developmental biology · 2023Article
- Differential and targeted vesiculation: pathologic cellular responses to elevated arterial pressure.Molecular and cellular biochemistry · 2022Review
- The promise of placental extracellular vesicles: models and challenges for diagnosing placental dysfunction in utero†.Biology of reproduction · 2021Review
- Role of dyslipidemia in the development of early-onset preeclampsia.Journal of advanced pharmaceutical technology & researchArticle
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
Small extracellular vesicles (sEVs) released from the extravillous trophoblast (EVT) are known to regulate uterine spiral artery remodeling during early pregnancy. The bioactivity and release of these sEVs differ under differing oxygen tensions and in aberrant pregnancy conditions. Whether the placental cell-derived sEVs released from the hypoxic placenta contribute to the pathophysiology of preeclampsia is not known. We hypothesize that, in response to low oxygen tension, the EVT packages a specific set of proteins in sEVs and that these released sEVs interact with endothelial cells to induce inflammation and increase maternal systemic blood pressure. Using a quantitative MS/MS approach, we identified 507 differentially abundant proteins within sEVs isolated from HTR-8/SVneo cells (a commonly used EVT model) cultured at 1% (hypoxia) compared with 8% (normoxia) oxygen. Among these differentially abundant proteins, 206 were up-regulated and 301 were down-regulated (P < 0.05), and they were mainly implicated in inflammation-related pathways. In vitro incubation of hypoxic sEVs with endothelial cells, significantly increased (P < 0.05) the release of GM-CSF, IL-6, IL-8, and VEGF, when compared with control (i.e. cells without sEVs) and normoxic sEVs. In vivo injection of hypoxic sEVs into pregnant rats significantly increased (P < 0.05) mean arterial pressure with increases in systolic and diastolic blood pressures. We propose that oxygen tension regulates the release and bioactivity of sEVs from EVT and that these sEVs regulate inflammation and maternal systemic blood pressure. This novel oxygen-responsive, sEVs signaling pathway, therefore, may contribute to the physiopathology of preeclampsia.
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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.