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Exosomal miR-145 and miR-885 regulate thrombosis in COVID-19 .

Jessica GambardellaUrna KansakarCelestino SarduVincenzo MessinaStanislovas S JankauskasRaffaele MarfellaPaolo MaggiXujun WangPasquale MoneGiuseppe PaolissoDaniela SorrientoGaetano Santulli
Published in: The Journal of pharmacology and experimental therapeutics (2022)
We hypothesized that exosomal microRNAs (miRNAs) could be implied in the pathogenesis of thromboembolic complications in COVID-19. We isolated circulating exosomes from COVID-19 patients and then we divided our population in two arms based on the D-dimer level on hospital admission. We observed that exosomal miR-145 and miR-885 significantly correlate with D-Dimer levels. Moreover, we demonstrate that human endothelial cells express the main cofactors needed for SARS-CoV-2 internalization, including ACE2, TMPRSS2, and CD-147. Interestingly, human endothelial cells treated with serum from COVID-19 patients release significantly less miR-145 and miR-885, exhibit increased apoptosis, and display significantly impaired angiogenetic properties compared to cells treated with non-COVID-19 serum. Taken together, our data indicate that exosomal miR-145 and miR-885 are essential in modulating thromboembolic events in COVID-19. Significance Statement In this work, we demonstrate for the first time that two specific microRNA (namely miR-145 and miR-885) contained in circulating exosomes are functionally involved in thromboembolic events in COVID-19. Our findings are especially relevant to the general audience when considering the emerging prominence of post-acute sequelae of COVID-19 systemic manifestations known as Long-COVID.
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