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Toro, Diana Mota V.
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da Silva-Neto, Pedro V.
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de Carvalho, Jonatan C. S. A.
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Fuzo, Carlos A. M.
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Perez, Malena M.
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Pimentel, Vinicius E.
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Fraga-Silva, Thais F. C.
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Oliveira, Camilla N. S. R.
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Caruso, Glaucia R.
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Vilela, Adriana F. L.
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Nobre-Azevedo, Pedro V.
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Defelippo-Felippe, Thiago V.
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Argolo, Jamille G. M. M.
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Degiovani, Augusto M.
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Ostini, Fatima M. R.
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Feitosa, Marley R. S.
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Parra, Rogerio S. C.
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Vilar, Fernando C. G.
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Gaspar, Gilberto G.
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da Rocha, Jose J. R.
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Feres, Omar P.
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Costa, Gabriel P.
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Maruyama, Sandra R. C.
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Russo, Elisa M. S.
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Fernandes, Ana Paula M.
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Santos, Isabel K. F. M.
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Malheiro, Adriana T.
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Sadikot, Ruxana T.
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Bonato, Vania L. D.
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Cardoso, Cristina R. B.
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Dias-Baruffi, Marcelo
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Trape, Atila A.
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Faccioli, Lucia H. A.
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Sorgi, Carlos A.
Número total de Autores: 34
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| Tipo de documento: | Artigo Científico |
| Fonte: | CELLS; v. 12, n. 15, p. 23-pg., 2023-08-01. |
| Resumo | |
SARS-CoV-2 infection triggers distinct patterns of disease development characterized by significant alterations in host regulatory responses. Severe cases exhibit profound lung inflammation and systemic repercussions. Remarkably, critically ill patients display a "lipid storm", influencing the inflammatory process and tissue damage. Sphingolipids (SLs) play pivotal roles in various cellular and tissue processes, including inflammation, metabolic disorders, and cancer. In this study, we employed high-resolution mass spectrometry to investigate SL metabolism in plasma samples obtained from control subjects (n = 55), COVID-19 patients (n = 204), and convalescent individuals (n = 77). These data were correlated with inflammatory parameters associated with the clinical severity of COVID-19. Additionally, we utilized RNAseq analysis to examine the gene expression of enzymes involved in the SL pathway. Our analysis revealed the presence of thirty-eight SL species from seven families in the plasma of study participants. The most profound alterations in the SL species profile were observed in patients with severe disease. Notably, a predominant sphingomyelin (SM d18:1) species emerged as a potential biomarker for COVID-19 severity, showing decreased levels in the plasma of convalescent individuals. Elevated SM levels were positively correlated with age, hospitalization duration, clinical score, and neutrophil count, as well as the production of IL-6 and IL-8. Intriguingly, we identified a putative protective effect against disease severity mediated by SM (d18:1/24:0), while ceramide (Cer) species (d18:1/24:1) and (d18:1/24:0)were associated with increased risk. Moreover, we observed the enhanced expression of key enzymes involved in the SL pathway in blood cells from severe COVID-19 patients, suggesting a primary flow towards Cer generation in tandem with SM synthesis. These findings underscore the potential of SM as a prognostic biomarker for COVID-19 and highlight promising pharmacological targets. By targeting sphingolipid pathways, novel therapeutic strategies may emerge to mitigate the severity of COVID-19 and improve patient outcomes. (AU) | |
| Processo FAPESP: | 20/08534-8 - Análise lipidômica empregando espectrometria de massas de alta resolução para determinação de perfil molecular em plasma de pacientes infectados por SARS-CoV-2 |
| Beneficiário: | Malena Martínez Pérez |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 15/00658-1 - Novos aspectos funcionais dos eicosanóides |
| Beneficiário: | Lúcia Helena Faccioli |
| Modalidade de apoio: | Auxílio à Pesquisa - Programa Equipamentos Multiusuários |
| Processo FAPESP: | 20/05270-0 - Papel da morte de células epiteliais alveolares humanas na inflamação causada pelo 2019-nCoV e comprovação por análise do transcriptoma de pacientes infectados |
| Beneficiário: | Vânia Luiza Deperon Bonato |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 20/05207-6 - Avaliação prospectiva da produção de mediadores lipídicos na resposta imune contra COVID-19: busca de biomarcadores e novos alvos terapêuticos na evolução da doença |
| Beneficiário: | Lúcia Helena Faccioli |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 21/04590-3 - Análise exploratória da lipidômica funcional na patofisiologia da COVID-19: alvos moleculares, metabolismo e reprogramação bioquímica por hipóxia |
| Beneficiário: | Carlos Arterio Sorgi |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 14/07125-6 - Novos aspectos funcionais dos eicosanóides |
| Beneficiário: | Lúcia Helena Faccioli |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |