{
  "abstract": "Introduction Successful pregnancy requires optimal uteroplacental vascular remodelling, driven by blood flow and characterized by vasodilation and structural changes to ensure adequate nutrient and oxygen supply to the placenta and fetus. Impaired remodelling can lead to pre-eclampsia and fetal growth restriction (FGR), increasing risks of maternal and fetal complications and long-term cardiovascular disease. Despite extensive research, the molecular and cellular mechanisms of pathophysiological uteroplacental remodelling remain poorly understood. Our lab previously demonstrated the adaptor protein Shc’s role in flow-mediated collateral expansion and atherosclerosis. Here, we investigate Shc’s role in uteroplacental vascular remodelling during pregnancy.Methods Endothelial-specific Shc knockout mice (ShcECKO) and littermate controls were time-mated, with fetuses harvested at embryonic day (E) 18.5. Uterine artery and fetal morphometrics, along with placental weights, were measured. Trophoblast invasion, a feature of spiral artery remodelling, was assessed via cytokeratin-8 staining. In vitro, shear stress and tensional force were applied to control and SHC-depleted human uterine endothelial cells (ECs) to study SHC’s mechanistic role in flow-mediated remodelling.Results ShcECKO mice exhibited significantly smaller uterine artery lumen area and circumference compared to controls. Trophoblast invasion was attenuated in the uterine spiral arteries from ShcECKO mice, suggesting diminished remodelling. Placentae and fetuses from ShcECKO mice were lighter, and fetuses from ShcECKO mice showed preferential growth of the brain over the rest of the body (brain sparing), a hallmark of asymmetric FGR. Exposure of SHC-depleted uterine ECs to shear stress and tensional force resulted in reduced mechano-activation of key signalling mediators.Conclusion Shc is a critical mechanotransducer in flow-mediated remodelling of the uteroplacental vasculature during pregnancy.",
  "authors": [
    {
      "affiliations": [
        "Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK"
      ],
      "name": "Vedanta Mehta"
    },
    {
      "affiliations": [
        "Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK"
      ],
      "name": "Feiran Zhang"
    },
    {
      "affiliations": [
        "Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK"
      ],
      "name": "Claire Aitken"
    },
    {
      "affiliations": [
        "Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK"
      ],
      "name": "Kar Lai Pang"
    },
    {
      "affiliations": [
        "Nuffield Department of Women’s and Reproductive Health, University of Oxford, Oxford, UK"
      ],
      "name": "Manu Vatish"
    },
    {
      "affiliations": [
        "Institute for Women’s Health, University College London, London, UK"
      ],
      "name": "Anna L David"
    },
    {
      "affiliations": [
        "Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK"
      ],
      "name": "John Reader"
    },
    {
      "affiliations": [
        "Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK"
      ],
      "name": "Ellie Tzima"
    }
  ],
  "title": "O2  Mechanical regulation of uteroplacental remodelling in pregnancy",
  "uid": "228f7ac1-f277-5b49-aae9-9cdf240e4435"
}