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WIN 55,212-2 shows anti-inflammatory and survival properties in human iPSC-derived cardiomyocytes infected with SARS-CoV-2

  • Luiz Guilherme H.S. Aragão
  • , Júlia T. Oliveira
  • , Jairo R. Temerozo
  • , Mayara A. Mendes
  • , José Alexandre Salerno
  • , Carolina S.G. Pedrosa
  • , Teresa Puig-Pijuan
  • , Carla P. Veríssimo
  • , Isis M. Ornelas
  • , Thayana Torquato
  • , Gabriela Vitória
  • , Carolina Q. Sacramento
  • , Natalia Fintelman-Rodrigues
  • , Suelen Da Silva Gomes Dias
  • , Vinicius Cardoso Soares
  • , Letícia R.Q. Souza
  • , Karina Karmirian
  • , Livia Goto-Silva
  • , Diogo Biagi
  • , Estela M. Cruvinel
  • Rafael Dariolli, Daniel R. Furtado, Patrícia T. Bozza, Helena L. Borges, Thiago M.L. Souza, Marília Zaluar P. Guimarães, Stevens K. Rehen

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can infect several organs, especially impacting respiratory capacity. Among the extrapulmonary manifestations of COVID-19 is myocardial injury, which is associated with a high risk of mortality. Myocardial injury, caused directly or indirectly by SARS-CoV-2 infection, can be triggered by inflammatory processes that lead to damage to the heart tissue. Since one of the hallmarks of severe COVID-19 is the "cytokine storm", strategies to control inflammation caused by SARS-CoV-2 infection have been considered. Cannabinoids are known to have anti-inflammatory properties by negatively modulating the release of pro-inflammatory cytokines. Herein, we investigated the effects of the cannabinoid agonist WIN 55,212-2 (WIN) in human iPSC-derived cardiomyocytes (hiPSC-CMs) infected with SARS-CoV-2. WIN did not modify angiotensin-converting enzyme II protein levels, nor reduced viral infection and replication in hiPSC-CMs. On the other hand, WIN reduced the levels of interleukins six, eight, 18 and tumor necrosis factor-alpha (TNF-a) released by infected cells, and attenuated cytotoxic damage measured by the release of lactate dehydrogenase (LDH). Our findings suggest that cannabinoids should be further explored as a complementary therapeutic tool for reducing inflammation in COVID-19 patients.

Original languageEnglish
Article numbere12262
JournalPeerJ
Volume9
DOIs
StatePublished - Oct 2021

Keywords

  • COVID-19
  • Cannabinoids
  • Human iPSC-derived cardiomyocytes
  • SARS-Cov-2
  • WIN 55,212-2

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