Mass Spectrometry-Based Proteomic Profiling of Thrombotic Material Obtained by Endovascular Thrombectomy in Patients with Ischemic Stroke

Int J Mol Sci. 2018 Feb 7;19(2):498. doi: 10.3390/ijms19020498.

Abstract

Thrombotic material retrieved from acute ischemic stroke (AIS) patients represents a valuable source of biological information. In this study, we have developed a clinical proteomics workflow to characterize the protein cargo of thrombi derived from AIS patients. To analyze the thrombus proteome in a large-scale format, we developed a workflow that combines the isolation of thrombus by endovascular thrombectomy and peptide chromatographic fractionation coupled to mass-spectrometry. Using this workflow, we have characterized a specific proteomic expression profile derived from four AIS patients included in this study. Around 1600 protein species were unambiguously identified in the analyzed material. Functional bioinformatics analyses were performed, emphasizing a clustering of proteins with immunological functions as well as cardiopathy-related proteins with blood-cell dependent functions and peripheral vascular processes. In addition, we established a reference proteomic fingerprint of 341 proteins commonly detected in all patients. Protein interactome network of this subproteome revealed protein clusters involved in the interaction of fibronectin with 14-3-3 proteins, TGFβ signaling, and TCP complex network. Taken together, our data contributes to the repertoire of the human thrombus proteome, serving as a reference library to increase our knowledge about the molecular basis of thrombus derived from AIS patients, paving the way toward the establishment of a quantitative approach necessary to detect and characterize potential novel biomarkers in the stroke field.

Keywords: biomarkers; endovascular therapy; ischemic stroke; proteomics; thrombus.

MeSH terms

  • Aged
  • Biomarkers / analysis
  • Brain Ischemia / metabolism*
  • Brain Ischemia / surgery
  • Endovascular Procedures
  • Gene Expression Profiling
  • Humans
  • Male
  • Mass Spectrometry
  • Middle Aged
  • Protein Interaction Mapping
  • Proteome / analysis
  • Proteomics*
  • Stroke / metabolism*
  • Stroke / surgery
  • Thrombectomy
  • Thrombosis / metabolism*
  • Thrombosis / surgery

Substances

  • Biomarkers
  • Proteome