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

• Main Authors: Roberto Muñoz, Enrique Santamaría, Idoya Rubio, Karina Ausín, Aiora Ostolaza, Alberto Labarga, Miren Roldán, Beatriz Zandio, Sergio Mayor, Rebeca Bermejo, Mónica Mendigaña, María Herrera, Nuria Aymerich, Jorge Olier, Jaime Gállego, Maite Mendioroz, Joaquín Fernández-Irigoyen
• Format: Article
• Language: English
• Published: MDPI AG 2018-02-01
• Series: International Journal of Molecular Sciences
• Subjects: ischemic stroke; proteomics; biomarkers; endovascular therapy; thrombus
• Online Access: http://www.mdpi.com/1422-0067/19/2/498

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.