Protein content of blood-derived extracellular vesicles: An approach to the pathophysiology of cerebral hemorrhage

Laso-García F, Piniella D, Gómez-de Frutos MC et al.  Front Cell Neurosci. 2023 Jan 19;16:1058546. doi: 10.3389/fncel.2022.1058546. eCollection 2022. PMID: 36776230


Introduction: Extracellular vesicles (EVs) participate in cell-to-cell paracrine signaling and can be biomarkers of the pathophysiological processes underlying disease. In intracerebral hemorrhage, the study of the number and molecular content of circulating EVs may help elucidate the biological mechanisms involved in damage and repair, contributing valuable information to the identification of new therapeutic targets.
Methods: The objective of this study was to describe the number and protein content of blood-derived EVs following an intracerebral hemorrhage (ICH). For this purpose, an experimental ICH was induced in the striatum of Sprague-Dawley rats and EVs were isolated and characterized from blood at baseline, 24 h and 28 days. The protein content in the EVs was analyzed by mass spectrometric data-dependent acquisition; protein quantification was obtained by sequential window acquisition of all theoretical mass spectra data and compared at pre-defined time points.
Results: Although no differences were found in the number of EVs, the proteomic study revealed that proteins related to the response to cellular damage such as deubiquitination, regulation of MAP kinase activity (UCHL1) and signal transduction (NDGR3), were up-expressed at 24 h compared to baseline; and that at 28 days, the protein expression profile was characterized by a higher content of the proteins involved in healing and repair processes such as cytoskeleton organization and response to growth factors (COR1B) and the regulation of autophagy (PI42B).
Discussion: The protein content of circulating EVs at different time points following an ICH may reflect evolutionary changes in the pathophysiology of the disease.

Funding: This work was supported by the Spanish Ministry of HealthCarlos III Health Institute (ISCIII) and the European Regional Development Fund (FEDER Funding) under grant PI17/01922 and PI20/00243, the Invictus Plus network under grant RD16/0019/0005, RICORS network under grant RD21/0006/0012, Miguel Servet under grant CPII20/00002 to MG-F; CP20/00024 to LO-O, Sara Borrell under grant CD19/00033 to MP-M, Ministerio de Universidades, Plan de Recuperación, Transformación y Resiliencia, Universidad Autónoma de Madrid under grant CA1/RSUE/2021-00753 to DP, and the Spanish Ministry of Health-Carlos III Health Institute (ISCIII) under grant FI18/00026 to FL-G, FI17/00188 to MG-F