Poster Presentation AUS-oMicS 2025

Glycome biosignature of peripheral blood mononuclear cells in patients with symptomatic coronary artery disease (120776)

Naomi Wattchow 1 2 3 , Anuk Indraratna 4 , Arun Everest-Dass 4 , Daniel Kolarich 4 , Joanne Tan 1 3 , Thalia Salagaras 3 , Lauren Sandeman 3 , Nicolle Packer 3 , Peter Psaltis 1 3 5 , Christina Bursill 1 3
  1. Adelaide Medical School, University of Adelaide, Adelaide, SA , Australia
  2. Flinders Medical Centre, SA Health, Bedford Park, SA , Australia
  3. SA Health and Medical Research Institute, Brighton, SA, Australia
  4. Institute for Biomedicine and Glycomics, Griffith University, Gold Coast, QLD, Australia
  5. Central Adelaide Local Health Network, SA Health, Adelaide, SA , Australia

 

Introduction:

Coronary artery disease (CAD) is a leading cause of human mortality marked by the buildup of plaque within the heart’s blood vessels. Despite current therapies, CAD patients experience recurrent events caused by the progression of residual plaques. Peripheral blood mononuclear cells (PBMCs) are involved in the pathophysiology of coronary atherosclerosis via low-density lipoprotein cholesterol uptake and deposition into plaques. VISION-CAD is a prospective multicentre study, designed to identify novel factors in the glycome which associate with coronary plaque progression as quantified on serial photon-counting computed tomography coronary angiography (PC-CTCA).

 

Method:

CAD participants undergo PC-CTCA and biobanking of PBMCs at baseline and 12-months follow-up. An optimised suspension-trapping (S-TrapTM) based sample preparation workflow was devised for the simultaneous release of N- and O-glycans from PBMC lysates. N-glycans were captured enzymatically with PNGase F, and O-glycans through chemical oxidative release. The purified glycans were analysed using porous graphitised carbon liquid chromatography coupled to electrospray ionisation tandem mass spectrometry (LC-MS) in negative mode. Glycans were identified based on their characteristic fragmentation patterns and quantified as relative abundances using the area-under-the-curve method. Coronary plaque analysis was performed using externally-validated, artificial intelligence-assisted software, AutoPlaque 3.0. We define plaque progression as ≥2% increase in percent atheroma volume (PAV) and regression as ≥2% decrease in PAV over one-year.

 

Results: In this proof-of-concept study, the PBMC glycome has been analysed for 15 patients: five CAD patients with plaque progression; five with plaque regression; and five healthy controls. The N-glycome of PBMCs predominantly contained oligomannose and sialylated structures, with bi-antennary doubly sialylated glycans, with and without core fucose, being the most abundant structures. We investigated both qualitative and quantitative differences in N- and O-glycan distributions across these groups to explore the potential role of the glycome in coronary atherosclerosis and identify novel therapeutic targets for CAD.