{
  "abstract": "Introduction Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are both associated with increased risk of cardiovascular involvement, predominantly, primary heart involvement and atherosclerotic cardiovascular disease (CVD) respectively. Cardiovascular MRI (CMR) studies have demonstrated vascular and non-ischaemic myocardial tissue abnormalities in both diseases. We have previously undertaken proteomic study in both SSc and RA cohorts that have been characterised using CMR. 1 2 It is unclear whether common or distinct mechanisms underlie the same CV processes. We aimed to identify whether common proteomic biomarkers in SSc and RA associate with vascular and myocardial tissue abnormalities and whether implicated pathways are shared.Material and Methods Seventy-eight participants from CONVAS (‘CONnective Tissue Disease and VASculitis Cohort’) and ELCASA (‘ELectrophysiology and CArdiac imaging in SclerodermA’)1 and 75 from the Coronary Artery Disease Evaluation in Rheumatoid Arthritis (CADERA) study cohorts underwent CV magnetic resonance (CMR) imaging. Using Olink Proximity Extension Assay, normalised protein expression was measured across cardiometabolic, CV II/III and inflammation panels in patient serum samples at the time of CMR. Bayesian generalised linear regression adjusted to age, gender, systolic blood pressure and body mass index was used to identify proteins associated with CMR parameters of vascular stiffness [aortic distensibility and stiffness] and myocardial oedema/fibrosis [native T1, myocardial extracellular volume and late gadolinium enhancement]. Subsequently, an expanded protein-protein interaction (PPI) network was created using an induced network approach (String-DB) with k-means clustering applied to identify enriched functional clusters that were then subjected to KEGG enrichment analysis. Shared proteins and pathways were identified through comparative analysis.Results Demographics and clinical characteristics of the two cohorts are presented in table 1. Fifty-four and 70 proteins were associated with CMR measures of vascular and myocardial tissue abnormalities the RA and SSc cohorts respectively. One protein, secretoglobin family 3A member 2 was associated with vascular abnormalities in both cohorts (aortic stiffness in RA and aortic distensibility in SSc) and 6 common proteins associated with myocardial tissue abnormalities (extracellular volume) in both cohorts – coagulation factor 11 (F11), fatty acid binding protein (FABP) 4, fibroblast growth factor (FGF) 19, insulin-like growth factor binding protein (IGFBP) 3, N-terminal pro-B natriuretic peptide (NTproBNP) and plasms serine protease inhibitor (SERPINA5) (figure 1). Expanded PPI network analysis identified clusters involved in JAK-STAT and ErbB signalling as common pathways in both cohorts.Conclusions This study indicates that there may be common protein biomarkers of CV processes across two distinct RMDs and offers preliminary insights into shared mechanistic pathways and potential therapeutic targets.References Plein S…Bunch MH. Ann. Rheum. Dis. 2020;79:1414–1422.Dumitru RB…Buch MH. RMD Open 2021;7(3):e001689.Abstract P.145 Table 1Demographics and clinical characteristics of RA and SSc patientsAbstract P.145 Figure 1Overlap of proteomic biomarkers of vascular and myocardial tissue abnormality in rheumatoid arthritis and systemic sclerosis",
  "authors": [
    {
      "affiliations": [
        "University of Manchester - Centre for Musculoskeletal Research, Manchester, United Kingdom"
      ],
      "name": "Rudresh Shukla"
    },
    {
      "affiliations": [
        "University of Manchester - Centre for Musculoskeletal Research, Manchester, United Kingdom"
      ],
      "name": "Amr Mohammed"
    },
    {
      "affiliations": [
        "University of Leeds - Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds, United Kingdom"
      ],
      "name": "Raluca Dumitru"
    },
    {
      "affiliations": [
        "University of Leeds - Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds, United Kingdom"
      ],
      "name": "Lesley-Anne Bissell"
    },
    {
      "affiliations": [
        "University of Leeds - Multidisciplinary Cardiovascular Research Centre (MCRC), Leeds, United Kingdom"
      ],
      "name": "Bara Erhayiem"
    },
    {
      "affiliations": [
        "University of Leeds - Multidisciplinary Cardiovascular Research Centre (MCRC), Leeds, United Kingdom"
      ],
      "name": "Graham Fent"
    },
    {
      "affiliations": [
        "University of Manchester - Division of Cardiovascular Sciences, Manchester, United Kingdom"
      ],
      "name": "Christopher Miller"
    },
    {
      "affiliations": [
        "University of Leeds - Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds, United Kingdom"
      ],
      "name": "Francesco Del Galdo"
    },
    {
      "affiliations": [
        "University of Leeds - Multidisciplinary Cardiovascular Research Centre (MCRC), Leeds, United Kingdom"
      ],
      "name": "Sven Plein"
    },
    {
      "affiliations": [
        "University of Manchester - Centre for Musculoskeletal Research, Manchester, United Kingdom"
      ],
      "name": "Darren Plant"
    },
    {
      "affiliations": [
        "University of Manchester - Centre for Musculoskeletal Research, Manchester, United Kingdom"
      ],
      "name": "Maya Buch"
    }
  ],
  "title": "P.145 Common proteomic biomarkers of vascular and myocardial tissue abnormalities in systemic sclerosis and rheumatoid arthritis",
  "uid": "9843df54-52a1-51b3-ba65-40148ee6a215"
}