{
  "abstract": "Introduction Gestation diabetes (GDM) is the transient development of diabetes during pregnancy, which typically resolves after delivery. It affects 1 in 20 UK pregnancies and predisposes both mother and child to early development of metabolic syndrome, type 2 diabetes (T2DM) and cardiovascular disease. The vascular wall is comprised of two key cell types: smooth muscle cells (SMC) which provide strength and integrity to the vessel, and endothelial cells (EC) which line the lumenal surface. Previous studies have shown that T2DM-SMC and -EC exhibit sustained phenotypic changes characterised by morphological, proliferative and senescence-associated aberrancies that remain even when cells are cultured in vitro, in the absence of diabetes-associated stimuli. However, it is unknown how long these patients had T2DM, and thus how long an exposure to the diabetic milieu is needed to induce persistent dysfunction. The present study is the first to characterise both primary SMC and EC phenotype from the umbilical cords of mothers with and without GDM, to examine whether phenotypic change can be induced in less than 9 months of diabetes.Methods Human umbilical artery SMC were isolated from GDM and non-diabetic (ND) donors via explant (n=3). Human umbilical vein EC were isolated from the same cords using enzyme digestion. Morphological characteristics were analysed using light microscopy and ImageJ. Senescence was measured by beta-galactosidase staining, changes in nuclear morphology and gene expression of senescence-associated cytokines by qPCR. Proliferation was measured by cell counting.Results GDM-SMC had a greater diversity in size and were on average 39.9% larger than ND-SMC, though they retained their spindle morphology. GDM-SMC had significantly higher senescence scores (69% increase) and incidence of multinucleation (43%), with reduced expression of LMNB1 and increased expression of interleukins IL8 (453% increase) and IL17A (1533% increase). There was no difference in the morphology or senescence of GDM-EC. In contrast to SMC, GDM-EC had a reduced expression of IL8 (85% decrease) and IL17A (58% decrease). Proliferative capacity was unchanged in either cell type.Conclusion GDM-SMC present evidence of persistent DNA damage after transient (maximum 9 months) exposure to the diabetic milieu, which is similar to the characteristics seen in T2DM-SMC. This study has revealed that transient exposure to diabetes in vivo is enough to impart persistent phenotypic change on SMC in vitro, but less so EC; highlighting cell-specific impacts of GDM. The effects on SMC may represent a potential mechanism by which GDM mothers and children are predisposed to vascular disease.",
  "authors": [
    {
      "affiliations": [
        "University of Bradford, Bradford, United Kingdom"
      ],
      "name": "Yaw Asare-Amankwah"
    },
    {
      "affiliations": [
        "University of Bradford, Bradford, United Kingdom"
      ],
      "name": "Shehryar Qureshi"
    },
    {
      "affiliations": [
        "University of Leeds, Leeds, United Kingdom"
      ],
      "name": "Marc Bailey"
    },
    {
      "affiliations": [
        "John Innes Centre, Norwich, United Kingdom"
      ],
      "name": "Anne Graham"
    },
    {
      "affiliations": [
        "University of Bradford, Bradford, United Kingdom"
      ],
      "name": "Andrew Tedder"
    },
    {
      "affiliations": [
        "University of Bradford, Bradford, United Kingdom"
      ],
      "name": "Kirsten Riches-Suman"
    }
  ],
  "title": "499 Gestational diabetes has divergent effects on vascular smooth muscle and endothelial cells from human umbilical cords",
  "uid": "ba217308-a8d0-5661-a66f-24e028b94b8d"
}