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


Journal

The Journal of pharmacology and experimental therapeutics
ISSN: 1521-0103
Titre abrégé: J Pharmacol Exp Ther
Pays: United States
ID NLM: 0376362

Informations de publication

Date de publication:
01 2023
Historique:
received: 14 03 2022
accepted: 09 05 2022
pmc-release: 01 01 2024
pubmed: 1 7 2022
medline: 27 12 2022
entrez: 30 6 2022
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 35772782
pii: jpet.122.001209
doi: 10.1124/jpet.122.001209
pmc: PMC9827505
doi:

Substances chimiques

MicroRNAs 0
MIRN145 microRNA, human 0
MIRN885 microRNA, human 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

109-115

Subventions

Organisme : NIDDK NIH HHS
ID : R01 DK123259
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK033823
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL159062
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL146691
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL144456
Pays : United States

Informations de copyright

Copyright © 2022 by The American Society for Pharmacology and Experimental Therapeutics.

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Auteurs

Jessica Gambardella (J)

Department of Medicine, Wilf Family Cardiovascular Research Institute (J.G., U.K., S.S.J., X.W., P.Mo.) and Department of Molecular Pharmacology, Einstein-Sinai Diabetes Research Center (ES-DRC), Institute for Neuroimmunology and Inflammation (INI), Fleischer Institute for Diabetes and Metabolism (FIDAM), Einstein Institute for Aging Research (G.S.), Albert Einstein College of Medicine, New York City, New York; Department of Advanced Biomedical Sciences, International Translational Research and Medical Education (ITME) Consortium, "Federico II" University, Naples, Italy (J.G., D.S., G.S.); Department of Advanced Medical and Surgical Sciences (C.S., R.M., P. Ma., G.P.), and Department of Mental and Physical Health and Preventive Medicine (P.Ma.) University of Campania, Naples, Italy; Infectious Disease Unit, "Sant'Anna and San Sebastiano" Hospital, Caserta, Italy (V.M.).

Urna Kansakar (U)

Department of Medicine, Wilf Family Cardiovascular Research Institute (J.G., U.K., S.S.J., X.W., P.Mo.) and Department of Molecular Pharmacology, Einstein-Sinai Diabetes Research Center (ES-DRC), Institute for Neuroimmunology and Inflammation (INI), Fleischer Institute for Diabetes and Metabolism (FIDAM), Einstein Institute for Aging Research (G.S.), Albert Einstein College of Medicine, New York City, New York; Department of Advanced Biomedical Sciences, International Translational Research and Medical Education (ITME) Consortium, "Federico II" University, Naples, Italy (J.G., D.S., G.S.); Department of Advanced Medical and Surgical Sciences (C.S., R.M., P. Ma., G.P.), and Department of Mental and Physical Health and Preventive Medicine (P.Ma.) University of Campania, Naples, Italy; Infectious Disease Unit, "Sant'Anna and San Sebastiano" Hospital, Caserta, Italy (V.M.).

Celestino Sardu (C)

Department of Medicine, Wilf Family Cardiovascular Research Institute (J.G., U.K., S.S.J., X.W., P.Mo.) and Department of Molecular Pharmacology, Einstein-Sinai Diabetes Research Center (ES-DRC), Institute for Neuroimmunology and Inflammation (INI), Fleischer Institute for Diabetes and Metabolism (FIDAM), Einstein Institute for Aging Research (G.S.), Albert Einstein College of Medicine, New York City, New York; Department of Advanced Biomedical Sciences, International Translational Research and Medical Education (ITME) Consortium, "Federico II" University, Naples, Italy (J.G., D.S., G.S.); Department of Advanced Medical and Surgical Sciences (C.S., R.M., P. Ma., G.P.), and Department of Mental and Physical Health and Preventive Medicine (P.Ma.) University of Campania, Naples, Italy; Infectious Disease Unit, "Sant'Anna and San Sebastiano" Hospital, Caserta, Italy (V.M.).

Vincenzo Messina (V)

Department of Medicine, Wilf Family Cardiovascular Research Institute (J.G., U.K., S.S.J., X.W., P.Mo.) and Department of Molecular Pharmacology, Einstein-Sinai Diabetes Research Center (ES-DRC), Institute for Neuroimmunology and Inflammation (INI), Fleischer Institute for Diabetes and Metabolism (FIDAM), Einstein Institute for Aging Research (G.S.), Albert Einstein College of Medicine, New York City, New York; Department of Advanced Biomedical Sciences, International Translational Research and Medical Education (ITME) Consortium, "Federico II" University, Naples, Italy (J.G., D.S., G.S.); Department of Advanced Medical and Surgical Sciences (C.S., R.M., P. Ma., G.P.), and Department of Mental and Physical Health and Preventive Medicine (P.Ma.) University of Campania, Naples, Italy; Infectious Disease Unit, "Sant'Anna and San Sebastiano" Hospital, Caserta, Italy (V.M.).

Stanislovas S Jankauskas (SS)

Department of Medicine, Wilf Family Cardiovascular Research Institute (J.G., U.K., S.S.J., X.W., P.Mo.) and Department of Molecular Pharmacology, Einstein-Sinai Diabetes Research Center (ES-DRC), Institute for Neuroimmunology and Inflammation (INI), Fleischer Institute for Diabetes and Metabolism (FIDAM), Einstein Institute for Aging Research (G.S.), Albert Einstein College of Medicine, New York City, New York; Department of Advanced Biomedical Sciences, International Translational Research and Medical Education (ITME) Consortium, "Federico II" University, Naples, Italy (J.G., D.S., G.S.); Department of Advanced Medical and Surgical Sciences (C.S., R.M., P. Ma., G.P.), and Department of Mental and Physical Health and Preventive Medicine (P.Ma.) University of Campania, Naples, Italy; Infectious Disease Unit, "Sant'Anna and San Sebastiano" Hospital, Caserta, Italy (V.M.).

Raffaele Marfella (R)

Department of Medicine, Wilf Family Cardiovascular Research Institute (J.G., U.K., S.S.J., X.W., P.Mo.) and Department of Molecular Pharmacology, Einstein-Sinai Diabetes Research Center (ES-DRC), Institute for Neuroimmunology and Inflammation (INI), Fleischer Institute for Diabetes and Metabolism (FIDAM), Einstein Institute for Aging Research (G.S.), Albert Einstein College of Medicine, New York City, New York; Department of Advanced Biomedical Sciences, International Translational Research and Medical Education (ITME) Consortium, "Federico II" University, Naples, Italy (J.G., D.S., G.S.); Department of Advanced Medical and Surgical Sciences (C.S., R.M., P. Ma., G.P.), and Department of Mental and Physical Health and Preventive Medicine (P.Ma.) University of Campania, Naples, Italy; Infectious Disease Unit, "Sant'Anna and San Sebastiano" Hospital, Caserta, Italy (V.M.).

Paolo Maggi (P)

Department of Medicine, Wilf Family Cardiovascular Research Institute (J.G., U.K., S.S.J., X.W., P.Mo.) and Department of Molecular Pharmacology, Einstein-Sinai Diabetes Research Center (ES-DRC), Institute for Neuroimmunology and Inflammation (INI), Fleischer Institute for Diabetes and Metabolism (FIDAM), Einstein Institute for Aging Research (G.S.), Albert Einstein College of Medicine, New York City, New York; Department of Advanced Biomedical Sciences, International Translational Research and Medical Education (ITME) Consortium, "Federico II" University, Naples, Italy (J.G., D.S., G.S.); Department of Advanced Medical and Surgical Sciences (C.S., R.M., P. Ma., G.P.), and Department of Mental and Physical Health and Preventive Medicine (P.Ma.) University of Campania, Naples, Italy; Infectious Disease Unit, "Sant'Anna and San Sebastiano" Hospital, Caserta, Italy (V.M.).

Xujun Wang (X)

Department of Medicine, Wilf Family Cardiovascular Research Institute (J.G., U.K., S.S.J., X.W., P.Mo.) and Department of Molecular Pharmacology, Einstein-Sinai Diabetes Research Center (ES-DRC), Institute for Neuroimmunology and Inflammation (INI), Fleischer Institute for Diabetes and Metabolism (FIDAM), Einstein Institute for Aging Research (G.S.), Albert Einstein College of Medicine, New York City, New York; Department of Advanced Biomedical Sciences, International Translational Research and Medical Education (ITME) Consortium, "Federico II" University, Naples, Italy (J.G., D.S., G.S.); Department of Advanced Medical and Surgical Sciences (C.S., R.M., P. Ma., G.P.), and Department of Mental and Physical Health and Preventive Medicine (P.Ma.) University of Campania, Naples, Italy; Infectious Disease Unit, "Sant'Anna and San Sebastiano" Hospital, Caserta, Italy (V.M.).

Pasquale Mone (P)

Department of Medicine, Wilf Family Cardiovascular Research Institute (J.G., U.K., S.S.J., X.W., P.Mo.) and Department of Molecular Pharmacology, Einstein-Sinai Diabetes Research Center (ES-DRC), Institute for Neuroimmunology and Inflammation (INI), Fleischer Institute for Diabetes and Metabolism (FIDAM), Einstein Institute for Aging Research (G.S.), Albert Einstein College of Medicine, New York City, New York; Department of Advanced Biomedical Sciences, International Translational Research and Medical Education (ITME) Consortium, "Federico II" University, Naples, Italy (J.G., D.S., G.S.); Department of Advanced Medical and Surgical Sciences (C.S., R.M., P. Ma., G.P.), and Department of Mental and Physical Health and Preventive Medicine (P.Ma.) University of Campania, Naples, Italy; Infectious Disease Unit, "Sant'Anna and San Sebastiano" Hospital, Caserta, Italy (V.M.).

Giuseppe Paolisso (G)

Department of Medicine, Wilf Family Cardiovascular Research Institute (J.G., U.K., S.S.J., X.W., P.Mo.) and Department of Molecular Pharmacology, Einstein-Sinai Diabetes Research Center (ES-DRC), Institute for Neuroimmunology and Inflammation (INI), Fleischer Institute for Diabetes and Metabolism (FIDAM), Einstein Institute for Aging Research (G.S.), Albert Einstein College of Medicine, New York City, New York; Department of Advanced Biomedical Sciences, International Translational Research and Medical Education (ITME) Consortium, "Federico II" University, Naples, Italy (J.G., D.S., G.S.); Department of Advanced Medical and Surgical Sciences (C.S., R.M., P. Ma., G.P.), and Department of Mental and Physical Health and Preventive Medicine (P.Ma.) University of Campania, Naples, Italy; Infectious Disease Unit, "Sant'Anna and San Sebastiano" Hospital, Caserta, Italy (V.M.).

Daniela Sorriento (D)

Department of Medicine, Wilf Family Cardiovascular Research Institute (J.G., U.K., S.S.J., X.W., P.Mo.) and Department of Molecular Pharmacology, Einstein-Sinai Diabetes Research Center (ES-DRC), Institute for Neuroimmunology and Inflammation (INI), Fleischer Institute for Diabetes and Metabolism (FIDAM), Einstein Institute for Aging Research (G.S.), Albert Einstein College of Medicine, New York City, New York; Department of Advanced Biomedical Sciences, International Translational Research and Medical Education (ITME) Consortium, "Federico II" University, Naples, Italy (J.G., D.S., G.S.); Department of Advanced Medical and Surgical Sciences (C.S., R.M., P. Ma., G.P.), and Department of Mental and Physical Health and Preventive Medicine (P.Ma.) University of Campania, Naples, Italy; Infectious Disease Unit, "Sant'Anna and San Sebastiano" Hospital, Caserta, Italy (V.M.) daniela.sorriento@unina.it.

Gaetano Santulli (G)

Department of Medicine, Wilf Family Cardiovascular Research Institute (J.G., U.K., S.S.J., X.W., P.Mo.) and Department of Molecular Pharmacology, Einstein-Sinai Diabetes Research Center (ES-DRC), Institute for Neuroimmunology and Inflammation (INI), Fleischer Institute for Diabetes and Metabolism (FIDAM), Einstein Institute for Aging Research (G.S.), Albert Einstein College of Medicine, New York City, New York; Department of Advanced Biomedical Sciences, International Translational Research and Medical Education (ITME) Consortium, "Federico II" University, Naples, Italy (J.G., D.S., G.S.); Department of Advanced Medical and Surgical Sciences (C.S., R.M., P. Ma., G.P.), and Department of Mental and Physical Health and Preventive Medicine (P.Ma.) University of Campania, Naples, Italy; Infectious Disease Unit, "Sant'Anna and San Sebastiano" Hospital, Caserta, Italy (V.M.).

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