Exosomal miR-145 and miR-885 Regulate Thrombosis in COVID-19

Jessica Gambardella, Urna Kansakar, Celestino Sardu, Vincenzo Messina, Stanislovas S. Jankauskas, Raffaele Marfella, Paolo Maggi, Xujun Wang, Pasquale Mone, Giuseppe Paolisso, Daniela Sorriento, Gaetano Santulli

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

We hypothesized that exosomal microRNAs could be implied in the pathogenesis of thromboembolic complications in coronavirus disease 2019 (COVID-19). We isolated circulating exosomes from patients with COVID-19, 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 the internalization of the "Severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2), including angiotensin converting enzyme 2, transmembrane protease serine 2, 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 with 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: This work demonstrates for the first time that two specific microRNAs (namely miR-145 and miR-885) contained in circulating exosomes are functionally involved in thromboembolic events in COVID-19. These 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.

Original languageEnglish (US)
Pages (from-to)109-115
Number of pages7
JournalThe Journal of pharmacology and experimental therapeutics
Volume384
Issue number1
DOIs
StatePublished - Jan 1 2023

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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