LTB4-Driven Inflammation and Increased Expression of ALOX5/ACE2 During Severe COVID-19 in Individuals With Diabetes
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
Texto Completo: | https://www.arca.fiocruz.br/handle/icict/49900 |
Resumo: | Inova Fiocruz/Fundac¸~ao Oswaldo Cruz to N.M.T. (VPPCB-005-FIO-20-2-75), Coordenac¸~ao de Aperfeic¸oamento de Pessoal de N ıvel Superior–Brazil (CAPES) under Finance Code 001 to I.B.-S., S.N., and J.S., Conselho Nacional de Desenvolvimento Cient ıfico e Tecnol ogico– Brazil (CNPq) (to I.B.-S., S.N., A.B., C.B., and M.B.-N.), and National Institutes of Health grants R01HL124159-01, DK122147-01A1 and AI149207A (to C.H.S.). |
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Bonyek-Silva, IcaroMachado, Antônio Fernando AraujoSilva, Thiago CerqueiraNunes, SaraCruz, Marcio Rivison SilvaSilva, JessicaSantos, Reinan LimaBarral, Aldina Maria do PradoOliveira, Pablo Rafael SilveiraKhouri, Antonio RicardoSerezani, C. HenriqueBrodskyn, Claudia IdaCaldas, Juliana RibeiroBarral Netto, ManoelBoaventura, VivianeTavares, Natalia Machado2021-11-19T19:54:47Z2021-11-19T19:54:47Z2021BONYEK-SILVA, Icaro et al. LTB4-Driven Inflammation and Increased Expression of ALOX5/ACE2 During Severe COVID-19 in Individuals With Diabetes. Diabetes, v. 70, p. 2021-2130, Sept. 2021.0012-1797https://www.arca.fiocruz.br/handle/icict/4990010.2337/db20-1260Inova Fiocruz/Fundac¸~ao Oswaldo Cruz to N.M.T. (VPPCB-005-FIO-20-2-75), Coordenac¸~ao de Aperfeic¸oamento de Pessoal de N ıvel Superior–Brazil (CAPES) under Finance Code 001 to I.B.-S., S.N., and J.S., Conselho Nacional de Desenvolvimento Cient ıfico e Tecnol ogico– Brazil (CNPq) (to I.B.-S., S.N., A.B., C.B., and M.B.-N.), and National Institutes of Health grants R01HL124159-01, DK122147-01A1 and AI149207A (to C.H.S.).This work was supported by the Inova Fiocruz/Fundação Oswaldo Cruz to N.M.T. (VPPCB-005-FIO-20-2-75), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior–Brazil (CAPES) under Finance Code 001 to I.B.-S., S.N., and J.S., Conselho Nacional de Desenvolvimento Cientıfico e Tecnologico–Brazil (CNPq) (to I.B.-S., S.N., A.B., C.B., and M.B.-N.), and National Institutes of Health grants R01HL124159-01, DK122147-01A1 and AI149207A (to C.H.S.).Oswaldo Cruz Foundation. Gonçalo Moniz Institute. Salvador, BA, Brazil / Federal University of Bahia. Medical School. Salvador, BA, Brazil.Salvador University. Salvador, BA, Brazil.Oswaldo Cruz Foundation. Gonçalo Moniz Institute. Salvador, BA, Brazil / Federal University of Bahia. Medical School. Salvador, BA, Brazil.Oswaldo Cruz Foundation. Gonçalo Moniz Institute. Salvador, BA, Brazil / Federal University of Bahia. Medical School. Salvador, BA, Brazil.Salvador University. Salvador, BA, Brazil / Ernesto Simões Filho Hospital. Critical Care Unit. Salvador, BA, Brazil.Oswaldo Cruz Foundation. Gonçalo Moniz Institute. Salvador, BA, Brazil / Federal University of Bahia. Medical School. Salvador, BA, Brazil.Oswaldo Cruz Foundation. Gonçalo Moniz Institute. Salvador, BA, Brazil / Federal University of Bahia. Pharmacy School. Salvador, BA, Brazil.Oswaldo Cruz Foundation. Gonçalo Moniz Institute. Salvador, BA, Brazil / Federal University of Bahia. Medical School. Salvador, BA, Brazil / National Institute of Science and Technology. Institute of Investigation in Immunology. São Paulo, SP, Brazil.Federal University of Bahia. Institute of Biological Sciences. Salvador, BA, Brazil.Oswaldo Cruz Foundation. Gonçalo Moniz Institute. Salvador, BA, Brazil / Federal University of Bahia. Medical School. Salvador, BA, Brazil.Vanderbilt University. Department of Medicine. Division of Infectious Diseases. Medical Center. Nashville, TN, USA.Oswaldo Cruz Foundation. Gonçalo Moniz Institute. Salvador, BA, Brazil / Federal University of Bahia. Medical School. Salvador, BA, Brazil / National Institute of Science and Technology. Institute of Investigation in Immunology. São Paulo, SP, Brazil.Salvador University. Salvador, BA, Brazil / Ernesto Simões Filho Hospital. Critical Care Unit. Salvador, BA, Brazil / São Rafael Hospital–Rede d’Or. Critical Care Unit. Salvador, BA, Brazil / Bahiana School of Medicine and Public Health. Salvador, BA, Brazil.Oswaldo Cruz Foundation. Gonçalo Moniz Institute. Salvador, BA, Brazil / Federal University of Bahia. Medical School. Salvador, BA, Brazil / National Institute of Science and Technology. Institute of Investigation in Immunology. São Paulo, SP, Brazil.Oswaldo Cruz Foundation. Gonçalo Moniz Institute. Salvador, BA, Brazil / Federal University of Bahia. Medical School. Salvador, BA, Brazil.Oswaldo Cruz Foundation. Gonçalo Moniz Institute. Salvador, BA, Brazil / Federal University of Bahia. Medical School. Salvador, BA, Brazil / National Institute of Science and Technology. Institute of Investigation in Immunology. São Paulo, SP, Brazil.Diabetes is a known risk factor for severe coronavirus disease 2019 (COVID-19), the disease caused by the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there is a lack of knowledge about the mechanisms involved in the evolution of COVID-19 in individuals with diabetes. We aimed to evaluate whether the chronic low-grade inflammation of diabetes could play a role in the development of severe COVID-19. We collected clinical data and blood samples of patients with and without diabetes hospitalized for COVID-19. Plasma samples were used to measure inflammatory mediators and peripheral blood mononuclear cells, for gene expression analysis of the SARS-CoV-2 main receptor system (ACE2/TMPRSS2), and for the main molecule of the leukotriene B4 (LTB4) pathway (ALOX5). We found that diabetes activates the LTB4 pathway and that during COVID-19 it increases ACE2/TMPRSS2 as well as ALOX5 expression. Diabetes was also associated with COVID-19–related disorders, such as reduced oxygen saturation as measured by pulse oximetry/fraction of inspired oxygen (FiO2) and arterial partial pressure of oxygen/FiO2 levels, and increased disease duration. In addition, the expressions of ACE2 and ALOX5 are positively correlated, with increased expression in patients with diabetes and COVID-19 requiring intensive care assistance. We confirmed these molecular results at the protein level, where plasma LTB4 is significantly increased in individuals with diabetes. In addition, IL-6 serum levels are increased only in individuals with diabetes requiring intensive care assistance. Together, these results indicate that LTB4 and IL-6 systemic levels, as well as ACE2/ALOX5 blood expression, could be early markers of severe COVID-19 in individuals with diabetes.engAmerican Diabetes AssociationSARS-CoV-2Síndrome Respiratória Aguda GraveCoronavirusDiabetesInflamaçãoSARS-CoV-2Severe Acute Respiratory SyndromeCoronavirusDiabetesInflammationLTB4-Driven Inflammation and Increased Expression of ALOX5/ACE2 During Severe COVID-19 in Individuals With Diabetesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83097https://www.arca.fiocruz.br/bitstream/icict/49900/1/license.txt36b51ef91c52b5338d9d29ba0cc807bcMD51ORIGINALSilva, Icaro Bonyek LTB4 - Driven....pdfSilva, Icaro Bonyek LTB4 - Driven....pdfapplication/pdf1969170https://www.arca.fiocruz.br/bitstream/icict/49900/2/Silva%2c%20Icaro%20Bonyek%20LTB4%20-%20Driven....pdf92d939ce144dd66a78f89db5fe9819b0MD52icict/499002023-03-15 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dc.title.pt_BR.fl_str_mv |
LTB4-Driven Inflammation and Increased Expression of ALOX5/ACE2 During Severe COVID-19 in Individuals With Diabetes |
title |
LTB4-Driven Inflammation and Increased Expression of ALOX5/ACE2 During Severe COVID-19 in Individuals With Diabetes |
spellingShingle |
LTB4-Driven Inflammation and Increased Expression of ALOX5/ACE2 During Severe COVID-19 in Individuals With Diabetes Bonyek-Silva, Icaro SARS-CoV-2 Síndrome Respiratória Aguda Grave Coronavirus Diabetes Inflamação SARS-CoV-2 Severe Acute Respiratory Syndrome Coronavirus Diabetes Inflammation |
title_short |
LTB4-Driven Inflammation and Increased Expression of ALOX5/ACE2 During Severe COVID-19 in Individuals With Diabetes |
title_full |
LTB4-Driven Inflammation and Increased Expression of ALOX5/ACE2 During Severe COVID-19 in Individuals With Diabetes |
title_fullStr |
LTB4-Driven Inflammation and Increased Expression of ALOX5/ACE2 During Severe COVID-19 in Individuals With Diabetes |
title_full_unstemmed |
LTB4-Driven Inflammation and Increased Expression of ALOX5/ACE2 During Severe COVID-19 in Individuals With Diabetes |
title_sort |
LTB4-Driven Inflammation and Increased Expression of ALOX5/ACE2 During Severe COVID-19 in Individuals With Diabetes |
author |
Bonyek-Silva, Icaro |
author_facet |
Bonyek-Silva, Icaro Machado, Antônio Fernando Araujo Silva, Thiago Cerqueira Nunes, Sara Cruz, Marcio Rivison Silva Silva, Jessica Santos, Reinan Lima Barral, Aldina Maria do Prado Oliveira, Pablo Rafael Silveira Khouri, Antonio Ricardo Serezani, C. Henrique Brodskyn, Claudia Ida Caldas, Juliana Ribeiro Barral Netto, Manoel Boaventura, Viviane Tavares, Natalia Machado |
author_role |
author |
author2 |
Machado, Antônio Fernando Araujo Silva, Thiago Cerqueira Nunes, Sara Cruz, Marcio Rivison Silva Silva, Jessica Santos, Reinan Lima Barral, Aldina Maria do Prado Oliveira, Pablo Rafael Silveira Khouri, Antonio Ricardo Serezani, C. Henrique Brodskyn, Claudia Ida Caldas, Juliana Ribeiro Barral Netto, Manoel Boaventura, Viviane Tavares, Natalia Machado |
author2_role |
author author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Bonyek-Silva, Icaro Machado, Antônio Fernando Araujo Silva, Thiago Cerqueira Nunes, Sara Cruz, Marcio Rivison Silva Silva, Jessica Santos, Reinan Lima Barral, Aldina Maria do Prado Oliveira, Pablo Rafael Silveira Khouri, Antonio Ricardo Serezani, C. Henrique Brodskyn, Claudia Ida Caldas, Juliana Ribeiro Barral Netto, Manoel Boaventura, Viviane Tavares, Natalia Machado |
dc.subject.other.pt_BR.fl_str_mv |
SARS-CoV-2 Síndrome Respiratória Aguda Grave Coronavirus Diabetes Inflamação |
topic |
SARS-CoV-2 Síndrome Respiratória Aguda Grave Coronavirus Diabetes Inflamação SARS-CoV-2 Severe Acute Respiratory Syndrome Coronavirus Diabetes Inflammation |
dc.subject.en.pt_BR.fl_str_mv |
SARS-CoV-2 Severe Acute Respiratory Syndrome Coronavirus Diabetes Inflammation |
description |
Inova Fiocruz/Fundac¸~ao Oswaldo Cruz to N.M.T. (VPPCB-005-FIO-20-2-75), Coordenac¸~ao de Aperfeic¸oamento de Pessoal de N ıvel Superior–Brazil (CAPES) under Finance Code 001 to I.B.-S., S.N., and J.S., Conselho Nacional de Desenvolvimento Cient ıfico e Tecnol ogico– Brazil (CNPq) (to I.B.-S., S.N., A.B., C.B., and M.B.-N.), and National Institutes of Health grants R01HL124159-01, DK122147-01A1 and AI149207A (to C.H.S.). |
publishDate |
2021 |
dc.date.accessioned.fl_str_mv |
2021-11-19T19:54:47Z |
dc.date.available.fl_str_mv |
2021-11-19T19:54:47Z |
dc.date.issued.fl_str_mv |
2021 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
BONYEK-SILVA, Icaro et al. LTB4-Driven Inflammation and Increased Expression of ALOX5/ACE2 During Severe COVID-19 in Individuals With Diabetes. Diabetes, v. 70, p. 2021-2130, Sept. 2021. |
dc.identifier.uri.fl_str_mv |
https://www.arca.fiocruz.br/handle/icict/49900 |
dc.identifier.issn.pt_BR.fl_str_mv |
0012-1797 |
dc.identifier.doi.none.fl_str_mv |
10.2337/db20-1260 |
identifier_str_mv |
BONYEK-SILVA, Icaro et al. LTB4-Driven Inflammation and Increased Expression of ALOX5/ACE2 During Severe COVID-19 in Individuals With Diabetes. Diabetes, v. 70, p. 2021-2130, Sept. 2021. 0012-1797 10.2337/db20-1260 |
url |
https://www.arca.fiocruz.br/handle/icict/49900 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
American Diabetes Association |
publisher.none.fl_str_mv |
American Diabetes Association |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da FIOCRUZ (ARCA) instname:Fundação Oswaldo Cruz (FIOCRUZ) instacron:FIOCRUZ |
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