Plasma Exosomal Proteomics: Unveiling Novel Biomarkers for Ischemic Stroke in the Context of Diabetes

ABSTRACT: Diabetes increases the risk of ischemic stroke and mortality. Exosomes, which are vesicles abundant of not only nucleic acids but also proteins, transmit stable cellular information and traverse the blood-brain barrier, emerge as promising biomarkers for brain injury and non-invasive monitoring. Investigating exosome-proteomics might unveil innovative therapeutic strategies for improving outcomes in diabetic stroke patients. Exosomes were isolated from the plasma of acute ischemic stroke patients with and without type 2 diabetes (n=10 each). Electron microscopy and flow cytometry were employed to analyze exosome morphology and markers, while nanoparticle tracking assessed concentration and size. Label-free quantitative proteomics and bioinformatics identified novel prognostic biomarkers. The CIBERSORTx and BRETIGEA tools were respectively used to elucidate immune and brain cell-specific protein expression patterns from exosomes. Diabetic stroke patients exhibited elevated fasting glucose, HbA1c, and neutrophil levels. Proteomic profiling revealed 95 differentially expressed proteins (21 up-regulated, 74 down-regulated). Functional enrichment analyses (GO and KEGG) associated diabetic stroke with disrupted oxygen/nitric oxide transport, cellular and glucose metabolism, and reactive oxygen species response. Protein-protein interaction network analysis highlighted the recombinant hemoglobin family (HBA1, HBA2, HBB), human β defensin (HBD), phosphofructokinase-1 liver type (PFKL), and aldehyde dehydrogenase 3 family member A2 (ALDH3A2) as key regulators. Diabetes altered exosomal contributions, diminishing signals from CD4 memory T cells and brain endothelial cells, while enhancing those from follicular helper T cells. These findings underscore the potential of exosome-based diagnostics and therapeutics for diabetic stroke, paving the way for innovative therapeutic strategies.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Cell, Blood Plasma

DISEASE(S): Type 2 Diabetes Mellitus

SUBMITTER: Haiping Zhao  

LAB HEAD: Haiping Zhao

PROVIDER: PXD068810 | Pride | 2026-04-13

REPOSITORIES: Pride