Oral Presentation 31st Annual Lorne Proteomics Symposium 2026

Sepsis Serum Profiling Identifies a Unique Proteomic Signature Associated with Diastolic Dysfunction (133172)

Harley R Robinson 1 2 , Simon R Foster 2 3 4 , Rebecca Fitzsimmons 1 , Eddie X Shen 5 6 , Amelia Livermore 5 , James E Hudson 1 4 , Jayesh Dhanani 1 5 6 7
  1. Cardiac Bioengineering, QIMR Berghofer Medical Research Institute , Herston, QLD, Australia
  2. Cardiac Drug Discovery, QIMR Berghofer, Herston, QLD, Australia
  3. Department of pharmacology, Monash University, Clayton, Vic, Australia
  4. School of Biomedical Sciences, The University of Queensland, St Lucia, QLD, Australia
  5. Department of Intensive Care Medicine, Royal Brisbane and Women’s Hospital, Herston, QLD, Australia
  6. Faculty of Health, Medicine and Behavioural Science, The University of Queensland, Herston, QLD, Australia
  7. Centre for Clinical Research, University of Queensland, Brisbane, QLD, Australia

Sepsis is a systemic hyperinflammatory response that leads to multi-organ failure and remains a leading cause of mortality. Cardiac complications, particularly diastolic dysfunction, contribute significantly to sepsis-related deaths, yet no targeted therapies exist, partly due to the lack of physiologically relevant human cardiac models.

To investigate protein drivers of sepsis-induced diastolic dysfunction, we collected serum from 10 healthy donors and 31 patients with varying severity of septic shock, stratified by vasoactive infusion score (VIS). We then used a proximity extension assay method, by Olink, to explore the relative abundance of 5,264 proteins through the Explore HT panel. Concurrently, we assessed the functional impact of septic sera on human cardiac organoids (hCOs) by measuring force, rate, and contraction kinetics through pixel tracking analysis of 10-second videos. Linear regression was used to correlate proteomic changes with functional outcomes and identify potential drivers of cardiac dysfunction.

Our analysis revealed two distinct sepsis groupings based on serum proteomic profiles, independent of severity stratification. These groupings were associated with cardiac stress markers (e.g., cTnI, NT-proBNP), inflammatory cytokines (e.g., IL-10), sepsis-specific biomarkers such as pentraxin-3 (PTX3), and increased apoptotic processes. In hCOs, diastolic dysfunction correlated with specific secreted factors, including cytokines, metalloproteinases, and growth factors, indicating potential drivers of sepsis-induced cardiac impairment. Notably, non-canonical circulating proteins of renal origin were also linked to dysfunction, suggesting a role for inter-organ crosstalk through atypical damage-associated signalling.

These findings identify a distinct serum proteomic signature associated with diastolic dysfunction in sepsis, highlighting potential biomarkers and therapeutic targets. Additionally, we demonstrate the utility of hCOs for modelling sepsis-related cardiac impairment, providing a foundation for future targeted interventions.