Lisinopril increases lung ACE2 levels and SARS-CoV-2 viral load and decreases inflammation but not disease severity in experimental COVID-19

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Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.contributorOswaldo Cruz Foundation-
Autor(es): dc.contributorHospital Israelita Albert Einstein-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorNational Institute of Allergy and Infectious Diseases-
Autor(es): dc.creatorSilva-Santos, Yasmin-
Autor(es): dc.creatorPagni, Roberta Liberato-
Autor(es): dc.creatorGamon, Thais Helena Martins-
Autor(es): dc.creatorde Azevedo, Marcela Santiago Pacheco-
Autor(es): dc.creatorBielavsky, Mônica-
Autor(es): dc.creatorDarido, Maria Laura Goussain-
Autor(es): dc.creatorde Oliveira, Danielle Bruna Leal-
Autor(es): dc.creatorde Souza, Edmarcia Elisa-
Autor(es): dc.creatorWrenger, Carsten-
Autor(es): dc.creatorDurigon, Edson Luiz-
Autor(es): dc.creatorLuvizotto, Maria Cecília Rui-
Autor(es): dc.creatorAckerman, Hans Christian-
Autor(es): dc.creatorMarinho, Claudio Romero Farias-
Autor(es): dc.creatorEpiphanio, Sabrina-
Autor(es): dc.creatorCarvalho, Leonardo José Moura-
Data de aceite: dc.date.accessioned2025-08-21T22:01:45Z-
Data de disponibilização: dc.date.available2025-08-21T22:01:45Z-
Data de envio: dc.date.issued2025-04-29-
Data de envio: dc.date.issued2023-12-31-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.3389/fphar.2024.1414406-
Fonte completa do material: dc.identifierhttps://hdl.handle.net/11449/300914-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/300914-
Descrição: dc.descriptionCOVID-19 causes more severe and frequently fatal disease in patients with pre-existing comorbidities such as hypertension and heart disease. SARS-CoV-2 virus enters host cells through the angiotensin-converting enzyme 2 (ACE2), which is fundamental in maintaining arterial pressure through the renin-angiotensin system (RAS). Hypertensive patients commonly use medications such as angiotensin-converting enzyme inhibitors (ACEi), which can modulate the expression of ACE2 and, therefore, potentially impact the susceptibility and severity of SARS-CoV-2 infection. Here we assessed whether treatment of ACE2-humanized (K18-hACE2) mice with the ACEi Lisinopril affects lung ACE2 levels and the outcome of experimental COVID-19. K18-hACE2 mice were treated for 21 days with Lisinopril 10 mg/kg and were then infected with 105 PFU of SARS-CoV-2 (Wuhan strain). Body weight, clinical score, respiratory function, survival, lung ACE2 levels, viral load, lung histology, and cytokine (IL-6, IL-33, and TNF-α) levels were assessed. Mice treated with Lisinopril for 21 days showed increased levels of ACE2 in the lungs. Infection with SARS-CoV-2 led to massive decrease in lung ACE2 levels at 3 days post-infection (dpi) in treated and untreated animals, but Lisinopril-treated mice showed a fast recovery (5dpi) of ACE2 levels. Higher ACE2 levels in Lisinopril-treated mice led to remarkably higher lung viral loads at 3 and 6/7dpi. Lisinopril-treated mice showed decreased levels of the pro-inflammatory cytokines IL-6 and TNF-α in the serum and lungs at 6/7dpi. Marginal improvements in body weight, clinical score and survival were observed in Lisinopril-treated mice. No differences between treated and untreated infected mice were observed in respiratory function and lung histology. Lisinopril treatment showed both deleterious (higher viral loads) and beneficial (anti-inflammatory and probably anti-constrictory and anti-coagulant) effects in experimental COVID-19. These effects seem to compensate each other, resulting in marginal beneficial effects in terms of outcome for Lisinopril-treated animals.-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)-
Descrição: dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-
Descrição: dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)-
Descrição: dc.descriptionFundação Oswaldo Cruz-
Descrição: dc.descriptionLaboratory of Malaria Cellular and Molecular Immunopathology Faculty of Pharmaceutical Sciences Department of Clinical and Toxicological Analysis University of São Paulo-
Descrição: dc.descriptionLaboratory of Malaria Research Oswaldo Cruz Institute Oswaldo Cruz Foundation-
Descrição: dc.descriptionImmunology Laboratory Heart Institute Faculty of Medicine University of São Paulo-
Descrição: dc.descriptionLaboratory of Clinical and Molecular Virology Institute of Biomedical Sciences Department of Microbiology University of São Paulo-
Descrição: dc.descriptionLaboratory of Experimental Immunoparasitology Institute of Biomedical Sciences Department of Parasitology University of São Paulo-
Descrição: dc.descriptionHospital Israelita Albert Einstein-
Descrição: dc.descriptionUnit for Drug Discovery Department of Parasitology Institute of Biomedical Sciences University of São Paulo-
Descrição: dc.descriptionSchool of Veterinary Medicine of Araçatuba São Paulo State University-
Descrição: dc.descriptionPhysiology Unit Laboratory of Malaria and Vector Research National Institute of Allergy and Infectious Diseases-
Descrição: dc.descriptionSchool of Veterinary Medicine of Araçatuba São Paulo State University-
Descrição: dc.descriptionFAPESP: 2020/06747-4 2022/13150-0 2020/06409-1 2023/05478-8 2015/26722-8 2020/12277-0-
Descrição: dc.descriptionCNPq: 316462/2021-7 302917/2019-5 403464/2023-4 304033/2021-9 301524/2019-0-
Descrição: dc.descriptionCAPES: 88887.509097/2020-00 88887.929469/2023-00-
Descrição: dc.descriptionFAPERJ: E−26/200.314/2022-
Descrição: dc.descriptionFundação Oswaldo Cruz: VPPCB-005-FIO-20-2-49-
Idioma: dc.languageen-
Relação: dc.relationFrontiers in Pharmacology-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectACEi-
Palavras-chave: dc.subjectangiotensin-converting enzyme inhibitors-
Palavras-chave: dc.subjectCOVID-19-
Palavras-chave: dc.subjectK18-hACE2-
Palavras-chave: dc.subjectlisinopril-
Palavras-chave: dc.subjectSARS-CoV-2-
Título: dc.titleLisinopril increases lung ACE2 levels and SARS-CoV-2 viral load and decreases inflammation but not disease severity in experimental COVID-19-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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