{
  "abstract": "The aorta is compliant and can change shape in response to blood pressure changes. With age, the aorta loses compliance due to elastin degradation and increased collagen deposition. This causes the aorta to become stiffer. Mechanosensitive vascular smooth muscle cells (VSMCs), sense these changes and further decreases aortic compliance.We use polyacrylamide hydrogels of tuneable stiffness to investigate VSMC matrix stiffness response. These studies have revealed that microtubule stability plays an important role in maintaining cell morphology and resisting deformational forces. Stabilisation of microtubules recovers VSMC matrix stiffness response.VSMC contraction, migration and proliferation are energy dependent processes but whether matrix stiffness influences metabolic switching remains unknown. In this study, VSMCs were grown on soft, healthy and disease/age mimicking hydrogels. After 2 days, VSMCs were harvested and analysed for metabolite changes using 1H NMR.Our analysis revealed that metabolite profile remained very similar between soft and healthy mimicking stiffness. However, clear differences existed between healthy and disease/age stiffness mimicking hydrogels. Enrichment analysis revealed that metabolomic changes linked to oxidative and inflammatory stress responses and increased mitochondrial dysfunction in response to matrix stiffness. To investigate whether microtubule stabilisation and destabilisation was involved in stiffness induced metabolite changes, we treated VSMCs with paclitaxel and colchicine. Our analysis revealed that paclitaxel treatment altered metabolic profile of VSMCs on disease/age mimicking hydrogels. Enrichment analysis revealed compensatory responses for redox and oxidative stress were upregulated and energy metabolism and amino acid metabolism were downregulated.Future work will include analysis of early passage and late passage cells to model cell ageing and identify metabolite changes associated with age. Additionally, these changes can be mapped against changes in matrix stiffness to identify metabolite markers of vascular ageing.",
  "authors": [
    {
      "affiliations": [
        "University of East Anglia, Norwich, United Kingdom"
      ],
      "name": "Oliver Steward"
    },
    {
      "affiliations": [
        "University of East Anglia, Norwich, United Kingdom"
      ],
      "name": "Trey Koev"
    },
    {
      "affiliations": [
        "University of East Anglia, Norwich, United Kingdom"
      ],
      "name": "Maria Marin"
    },
    {
      "affiliations": [
        "University of East Anglia, Norwich, United Kingdom",
        "Royal Ventrinary College, London, United Kingdom"
      ],
      "name": "Derek Warren"
    }
  ],
  "title": "290 Defining metabolism changes during vascular smooth muscle cell matrix stiffness response",
  "uid": "41c397f5-ba0a-54e0-b50e-9177f5396890"
}