Proteomic Analysis of Equine Plasma and Peritoneal Fluid in Strangulating Small Intestinal Disease

Equine colic caused by ischaemic insult to the small intestine (SI) is commonly encountered clinically and carries a poor prognosis for survival, particularly if resection of the affected bowel is required. Total plasma and peritoneal fluid (PF) protein is routinely measured during clinical investigation, but is non‐specific for primary aetiology or prognosis. Changes in PF protein concentration and composition may precede those in the peripheral blood, but to the authors' knowledge the proteome of equine PF has not been reported. Blood plasma and PF from eight horses diagnosed with strangulating SI disease (SSID) and four horses euthanised for conditions unrelated to the gastrointestinal system were analysed using label‐free quantitative mass spectrometry. 350 proteins were identified in PF of control horses, 479 in PF from horses with SSID. 123 proteins were significantly differentially expressed (DE) between SSID and control horses (p<0.05, ≥2 fold change, >1 peptide). This reduced to 45 when adjusted for false discovery rate (q<0.05). 254 proteins were identified in plasma, 13 of which were DE between SSID and control horses (p<0.05, ≥2 fold change, >1 peptide). Six proteins were common to both fluid types. Four plasma proteins and 12 PF proteins were DE between SSID horses which survived to hospital discharge and those which did not. No proteins were common to both fluids. Of these 12 PF proteins, two showed significantly increased DE in both SSID horses versus controls and between non‐survivors and survivors and ten showed significantly lower DE in SSID horses relative to controls and between non‐survivors and survivors (Table 1). Relationships between significant proteins and associated pathways were investigated using the databases STRING, PANTHER and Ingenuity Pathway Analysis. The most significant canonical pathway identified for SSID versus controls for both plasma and PF and between survivors and non‐survivors for PF was LXR/RXR activation, indicating a potential link between altered lipid metabolism and inflammatory signalling in SSID. This is the first study to describe the equine PF proteome and to compare changes between healthy and diseased states. We have demonstrated a greater abundance of DE proteins in PF than plasma in response to SSID and DE proteins between fluid types and survivors and non‐survivors. We have identified twelve PF proteins (ten significantly reduced and two significantly increased in expression) associate with non‐survival to hospital discharge in horses with SSID. Further analyses will allow us to more fully understanding the pathophysiology of this disease, validate the utility of these proteins as biomarkers of prognosis following surgery and explore the potential of targeting the LXR/RXR pathway therapeutically. Support or Funding Information University of Liverpool MBI Departmental Research Support Budget University of Liverpool Technology Directorate Voucher Scheme This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .