Proteomic analysis of extracellular vesicles enriched serum associated with future ischemic stroke

Sci Rep. 2021 Dec 15;11(1):24024. doi: 10.1038/s41598-021-03497-0.

Abstract

Identifying new biomarkers beyond the established risk factors that make it possible to predict and prevent ischemic stroke has great significance. Extracellular vesicles are powerful cell‒cell messengers, containing disease-specific biomolecules, which makes them powerful diagnostic candidates. Therefore, this study aimed to identify proteins derived from extracellular vesicles enriched serum related to future ischemic stroke events, using a proteomic method. Of Japanese subjects who voluntarily participated in health checkups at our institute a number of times, 10 subjects (6 males and 4 females, age: 64.2 ± 3.9 years) who developed symptomatic ischemic stroke (7.3 ± 4.4 years' follow-up) and 10 age‒sex matched controls without brain lesions (6.7 ± 2.8 years' follow-up) were investigated. Extracellular vesicles enriched fractions were derived from serum collected at the baseline visit. Differentially expressed proteins were evaluated using isobaric tagging for relative and absolute protein quantification (iTRAQ)-based proteomic analysis. Of the 29 proteins identified, alpha-2-macroglobulin, complement C1q subcomponent subunit B, complement C1r subcomponent, and histidine-rich glycoprotein were significantly upregulated (2.21-, 2.15-, 2.24-, and 2.16-fold, respectively) in subjects with future ischemic stroke, as compared with controls. Our study supports the concept of serum-derived extracellular vesicles enriched fractions as biomarkers for new-onset stroke. These proteins may be useful for prediction or for targeted therapy.

MeSH terms

  • Aged
  • Biomarkers* / blood
  • Chromatography, Liquid
  • Comorbidity
  • Disease Susceptibility
  • Enzyme-Linked Immunosorbent Assay
  • Extracellular Vesicles / metabolism*
  • Female
  • Humans
  • Ischemic Stroke / diagnosis
  • Ischemic Stroke / etiology
  • Ischemic Stroke / metabolism*
  • Male
  • Middle Aged
  • Prognosis
  • Proteome*
  • Proteomics* / methods
  • Risk Factors
  • Tandem Mass Spectrometry

Substances

  • Biomarkers
  • Proteome