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.
Highlights
Stroke represents one of the top causes of mortality and adult disability worldwide [1]
We have used thrombi from four acute ischemic stroke (AIS) patients (Table 1) with the aim of obtaining a deep insight into the protein cargo and protein function of the thrombotic material isolated by endovascular thrombectomy
We used a discovery platform combining endovascular thrombectomy, qualitative proteomics, and physical/functional interaction data to determine the molecular composition of thrombi of human origin in ischemic stroke
Summary
Stroke represents one of the top causes of mortality and adult disability worldwide [1]. Regardless of the significant diagnostic effort in the clinical setting, up to 30% of stroke patients are discharged with an undetermined or unknown etiology diagnosis [3]. Blood-based biomarkers have arisen as promising tools to help in the diagnosis of stroke etiology. These biomarkers still lack sufficient sensitivity and specificity to be implemented in the clinical setting [4]. That will be most helpful to identify novel blood biomarkers with better predictive values in the stroke field [5]
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