Exosomal miR-145 and miR-885 regulate thrombosis in COVID-19 .
Jessica GambardellaUrna KansakarCelestino SarduVincenzo MessinaStanislovas S JankauskasRaffaele MarfellaPaolo MaggiXujun WangPasquale MoneGiuseppe PaolissoDaniela SorrientoGaetano SantulliPublished 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.
Keyphrases
- sars cov
- cell proliferation
- long non coding rna
- coronavirus disease
- endothelial cells
- long noncoding rna
- respiratory syndrome coronavirus
- oxidative stress
- stem cells
- healthcare
- mesenchymal stem cells
- atrial fibrillation
- emergency department
- liver failure
- machine learning
- cell death
- pulmonary embolism
- bone marrow
- electronic health record
- hepatitis b virus
- signaling pathway
- deep learning
- artificial intelligence
- data analysis