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

tetano

Editor, Senior Moderator
PeerJ


. 2021 Oct 8;9:e12262.
doi: 10.7717/peerj.12262. eCollection 2021.
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[SUP] #[/SUP][SUP] 1 [/SUP], Júlia T Oliveira[SUP] #[/SUP][SUP] 1 [/SUP], Jairo R Temerozo[SUP] 2 3 [/SUP], Mayara A Mendes[SUP] 1 [/SUP], José Alexandre Salerno[SUP] 4 [/SUP], Carolina S G Pedrosa[SUP] 1 [/SUP], Teresa Puig-Pijuan[SUP] 1 5 [/SUP], Carla P Veríssimo[SUP] 4 [/SUP], Isis M Ornelas[SUP] 1 [/SUP], Thayana Torquato[SUP] 1 [/SUP], Gabriela Vitória[SUP] 1 [/SUP], Carolina Q Sacramento[SUP] 3 6 [/SUP], Natalia Fintelman-Rodrigues[SUP] 3 6 [/SUP], Suelen da Silva Gomes Dias[SUP] 6 [/SUP], Vinicius Cardoso Soares[SUP] 6 7 [/SUP], Letícia R Q Souza[SUP] 1 [/SUP], Karina Karmirian[SUP] 1 4 [/SUP], Livia Goto-Silva[SUP] 1 [/SUP], Diogo Biagi[SUP] 8 [/SUP], Estela M Cruvinel[SUP] 8 [/SUP], Rafael Dariolli[SUP] 8 9 [/SUP], Daniel R Furtado[SUP] 1 [/SUP], Patrícia T Bozza[SUP] 6 [/SUP], Helena L Borges[SUP] 4 [/SUP], Thiago M L Souza[SUP] 3 6 [/SUP], Marília Zaluar P Guimarães[SUP] 1 4 [/SUP], Stevens K Rehen[SUP] 1 10 [/SUP]



Affiliations

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-α) 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.

Keywords: COVID-19; Cannabinoids; Human iPSC-derived cardiomyocytes; SARS-Cov-2; WIN 55,212-2.
 
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