{
  "abstract": "Coronary artery disease (CAD) is a leading cause of global morbidity and mortality.1 In CAD, atherosclerosis narrows the coronary arteries leading to myocardial ischemia thence impaired systolic and diastolic cardiac function. While cytokines and oxidative stress are well recognised pathogenic mediators, their interaction and contribution to cardiac cellular dysfunction remains unclear. To elucidate this, we measured the effect of clinically relevant cytokine concentrations on oxidative stress in cardiac myoblasts.In accordance with local and IRAS (ID: 247341) ethical approval, preoperative serum samples were collected from patients scheduled for coronary revascularisation surgery. Serum interleukin-6 (IL-6), -10 (IL-10), -11 (IL-11) and tumour necrosis factor alpha (TNF-1) concentrations were measured using high-sensitivity ELISA (Abcam, UK & Invitrogen, USA). Cardiac myoblasts (H9c2) were incubated with these cytokines for 1 hour then loaded with CM-DCFDA for photometric measurement of oxidative stress.Average IL-6, IL-11, IL-10 and TNF-1 concentrations were 9.1 1 1.36, 1.46 1 0.26, 4.21 1 0.59 and 2.70 1 0.61 pg/mL, respectively. At these, and supra-pathological concentrations, only TNF-1 produced a significant increase in DCFDA fluorescence. For instance, at a concentration of 1 ng/mL, TNF-1 increased fluorescence by 111.28 ± 19.56% (n = 8, p < 0.001). This effect was abolished in the presence of N-acetyl cysteine and attenuated by the NADPH oxidase inhibitor VAS3947 and xanthine oxidoreductase inhibitor Febuxostat.These data suggest that at clinically relevant concentrations, TNF-1, but not IL-6, IL-11 or IL-10 can increase oxidative stress in cardiac myoblasts. This oxidative effect is at least partially dependent on NADPH oxidase and xanthine oxidoreductase. Our next experiments will determine whether these findings can be reproduced in primary and iPSC-derived cells and probe the contribution of mitochondrial dysfunction.Reference Centre’s for Disease Control and Prevention. (2023). Heart disease statistics and maps. https://www.cdc.gov/heartdisease/statistical_reports.htm",
  "authors": [
    {
      "affiliations": [
        "Biomedical Research and Innovation Centre, School of Science, Engineering and Environment, The University of Salford, Manchester, M5 4WT"
      ],
      "name": "Bethan Samphire-Noden"
    },
    {
      "affiliations": [
        "Biomedical Research and Innovation Centre, School of Science, Engineering and Environment, The University of Salford, Manchester, M5 4WT"
      ],
      "name": "Alicia Staley"
    },
    {
      "affiliations": [
        "Biomedical Research and Innovation Centre, School of Science, Engineering and Environment, The University of Salford, Manchester, M5 4WT"
      ],
      "name": "Matthew Jones"
    },
    {
      "affiliations": [
        "Biomedical Research and Innovation Centre, School of Science, Engineering and Environment, The University of Salford, Manchester, M5 4WT"
      ],
      "name": "Sarah Withers"
    },
    {
      "affiliations": [
        "Lancashire Cardiac Centre, Blackpool Victoria Hospital, FY3 8NR"
      ],
      "name": "Mohamad Nidal Bittar"
    },
    {
      "affiliations": [
        "Biomedical Research and Innovation Centre, School of Science, Engineering and Environment, The University of Salford, Manchester, M5 4WT"
      ],
      "name": "David Greensmith"
    }
  ],
  "title": "P28  The cellular basis of coronary artery disease; do clinically relevant cytokine concentrations elevate oxidative stress in cardiac myoblasts?",
  "uid": "6e974fae-637d-5f0a-ae86-cef79efd96c2"
}