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Neonatal Micro-RNA Profile Determines Endothelial Function in Offspring of Hypertensive Pregnancies.
Yu, Grace Z; Reilly, Svetlana; Lewandowski, Adam J; Aye, Christina Y L; Simpson, Lisa J; Newton, Laura; Davis, Esther F; Zhu, Sha J; Fox, Willow R; Goel, Anuj; Watkins, Hugh; Channon, Keith M; Watt, Suzanne M; Kyriakou, Theodosios; Leeson, Paul.
Afiliación
  • Yu GZ; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
  • Reilly S; Stem Cell Research, Radcliffe Department of Medicine, Nuffield Division of Clinical Laboratory Sciences and NHS Blood and Transplant, University of Oxford, Oxford, UK.
  • Lewandowski AJ; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
  • Aye CYL; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
  • Simpson LJ; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
  • Newton L; Nuffield Department of Obstetrics & Gynaecology, Medical Sciences Division, University of Oxford, Oxford, UK.
  • Davis EF; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
  • Zhu SJ; Stem Cell Research, Radcliffe Department of Medicine, Nuffield Division of Clinical Laboratory Sciences and NHS Blood and Transplant, University of Oxford, Oxford, UK.
  • Fox WR; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
  • Goel A; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
  • Watkins H; Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Channon KM; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
  • Watt SM; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
  • Kyriakou T; Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Leeson P; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Hypertension ; 72(4): 937-945, 2018 10.
Article en En | MEDLINE | ID: mdl-30287978
Offspring of hypertensive pregnancies are at increased risk of developing hypertension in adulthood. In the neonatal period they display endothelial cell dysfunction and altered microvascular development. MicroRNAs, as important endothelial cellular regulators, may play a role in this early endothelial dysfunction. Therefore we identified differential microRNA patterns in endothelial cells from offspring of hypertensive pregnancies and determined their role in postnatal vascular cell function. Studies were performed on human umbilical vein endothelial cell (HUVECs) samples from 57 pregnancies. Unbiased RNA-sequencing identified 30 endothelial-related microRNAs differentially expressed in HUVECs from hypertensive compared to normotensive pregnancies. Quantitative reverse transcription PCR (RT-qPCR) confirmed a significant higher expression level of the top candidate, miR-146a. Combined miR-146a targeted gene expression and pathway analysis revealed significant alterations in genes involved in inflammation, angiogenesis and immune response in the same HUVECs. Elevated miR-146a expression level at birth identified cells with reduced ability for in vitro vascular tube formation, which was rescued by miR-146a inhibition. In contrast, miR-146a overexpression significantly reduced vascular tube formation in HUVECs from normotensive pregnancies. Finally, we confirmed that mir146a levels at birth predicted in vivo microvascular development during the first three postnatal months. Offspring of hypertensive pregnancy have a distinct endothelial regulatory microRNA profile at birth, which is related to altered endothelial cell behaviour, and predicts patterns of microvascular development during the first three months of life. Modification of this microRNA profile in vitro can restore impaired vascular cell function.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vasos Sanguíneos / Endotelio Vascular / MicroARNs / Hipertensión Inducida en el Embarazo / Microvasos Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Adult / Female / Humans / Male / Newborn / Pregnancy País/Región como asunto: Europa Idioma: En Revista: Hypertension Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vasos Sanguíneos / Endotelio Vascular / MicroARNs / Hipertensión Inducida en el Embarazo / Microvasos Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Adult / Female / Humans / Male / Newborn / Pregnancy País/Región como asunto: Europa Idioma: En Revista: Hypertension Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos