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

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 384; no. 1; pp. 109 - 115
• Main Authors: Gambardella, Jessica, Kansakar, Urna, Sardu, Celestino, Messina, Vincenzo, Jankauskas, Stanislovas S., Marfella, Raffaele, Maggi, Paolo, Wang, Xujun, Mone, Pasquale, Paolisso, Giuseppe, Sorriento, Daniela, Santulli, Gaetano
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2023; The American Society for Pharmacology and Experimental Therapeutics
• Subjects: COVID-19 - complications; Endothelial Cells; Exosomes - metabolism; Humans; MicroRNAs - genetics; MicroRNAs - metabolism; Post-Acute COVID-19 Syndrome - genetics; Post-Acute COVID-19 Syndrome - metabolism; SARS-CoV-2; Special Section on Non-Coding RNAs in Clinical Practice: From Biomarkers to Therapeutic Tools; Thrombosis - genetics; Thrombosis - metabolism; Thrombosis - virology; COVID-19; HUVEC; miRNA; TF; vWF
• ISSN: 0022-3565; 1521-0103; 1521-0103
• DOI: 10.1124/jpet.122.001209

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. 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.