Scientific publications
Transcriptomic Analysis of Extracellular Vesicles in the Search for Novel Plasma and Thrombus Biomarkers of Ischemic Stroke Etiologies. Scientific Publication
Florencio J D M Machado 1 2 , Juan Marta-Enguita 1 2 3 , Susan U Gómez 1 , Jose A Rodriguez 1 2 4 , José Antonio Páramo-Fernández 1 2 4 5 , María Herrera 2 3 6 , Beatriz Zandio 3 6 , Nuria Aymerich 3 6 , Roberto Muñoz 3 6 , Rebeca Bermejo 7 , Javier Marta-Moreno 3 8 , Begoña López 2 4 9 , Arantxa González 2 4 9 10 , Carmen Roncal 1 2 4 , Josune Orbe 1 2 3
Abstract
Accurate etiologic diagnosis provides an appropriate secondary prevention and better prognosis in ischemic stroke (IS) patients; still, 45% of IS are cryptogenic, urging us to enhance diagnostic precision.
We have studied the transcriptomic content of plasma extracellular vesicles (EVs) (n = 21) to identify potential biomarkers of IS etiologies. The proteins encoded by the selected genes were measured in the sera of IS patients (n = 114) and in hypertensive patients with (n = 78) and without atrial fibrillation (AF) (n = 20). IGFBP-2, the most promising candidate, was studied using immunohistochemistry in the IS thrombi (n = 23) and atrium of AF patients (n = 13). In vitro, the IGFBP-2 blockade was analyzed using thromboelastometry and endothelial cell cultures.
We identified 745 differentially expressed genes among EVs of cardioembolic, atherothrombotic, and ESUS groups. From these, IGFBP-2 (cutoff > 247.6 ng/mL) emerged as a potential circulating biomarker of embolic IS [OR = 8.70 (1.84-41.13) p = 0.003], which was increased in patients with AF vs. controls (p < 0.001) and was augmented in cardioembolic vs. atherothrombotic thrombi (p < 0.01). Ex vivo, the blockage of IGFBP-2 reduced clot firmness (p < 0.01) and lysis time (p < 0.001) and in vitro, diminished endothelial permeability (p < 0.05) and transmigration (p = 0.06). IGFBP-2 could be a biomarker of embolic IS and a new therapeutic target involved in clot formation and endothelial dysfunction.
CITATION Int J Mol Sci. 2024 Apr 16;25(8):4379. doi: 10.3390/ijms25084379
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