Extracellular vesicles from post-COVID-19 patients alter endothelial function under protein restriction

Autor(es)

Bobato, Geiza Rafaela ; Rocha, Juliana Quinholi ; Guizoni, Daniele Mendes ; Nobrega, Natalia Ribeiro Cabacinha ; de Moura, Ludmilla David ; Rocha, Matheus Lavorenti ; Velloso, Licio Augusto ; Carneiro, Everardo Magalhaes ; Antunes-Correa, Ligia de Moraes ; Davel, Ana Paula

• Tipo de documento: Artigo Científico
• Fonte: AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY; v. 329, n. 4, p. 9-pg., 2025-10-29.

Resumo

The COVID-19 pandemic worsened global food insecurity and malnutrition. Protein restriction increases the risk of poor COVID-19 outcomes and cardiovascular disease. Post-COVID-19 syndrome remains a public health concern, although its underlying mechanisms are not yet fully understood. Extracellular vesicles (EVs), released by most cell types in response to infections, have been implicated in endothelial dysfunction during the post-COVID phase. We hypothesized that EV contribute to endothelial cell (EC) dysfunction in long-term COVID-19, particularly in the setting of protein malnutrition. Circulating EVs were isolated from patients at 1 and 6 months (mo) after hospital discharge due to severe COVID-19. Endothelial relaxation was assessed in mouse aortas after a 3-mo normoprotein or low-protein diet (LP). LP feeding reduced endothelium-dependent relaxation to acetylcholine, but EVs from post-COVID patients (1 and 6 mo) restored endothelium-dependent relaxation. This EV effect was abolished by catalase, but not by l-NAME (a nitric oxide synthase inhibitor) or indomethacin (a cyclooxygenase inhibitor). Aortas from LP mice incubated with post-COVID EVs exhibited reduced catalase expression and increased 4-hydroxynonenal (4-HNE) adducts. In vitro amino acid restriction increased EC death (Hoechst/Pi), and reduced nitric oxide (Diaminofluorescein-FM diacetato) and H2O2 (Amplex red) levels. Incubation with post-COVID EVs for 24 h increased H2O2 only in amino acid-restricted EC. EVs had no significant effect on acetylcholine-induced relaxation in normoprotein-fed mice or on EC parameters in vitro under control conditions. These findings suggest that EVs from patients 1 and 6 mo after severe COVID-19 impact aortic endothelial function by increasing H2O2 contribution under conditions of malnutrition. NEW & NOTEWORTHY Our study demonstrated that circulating extracellular vesicles (EVs) from patients 1 and 6 mo after severe COVID-19 altered endothelial function under protein restriction but not in healthy vessels. Post-COVID EVs enhanced the contribution of H2O2 to endothelium-dependent relaxation, associated with reduced catalase and increased 4-HNE-modified protein expression. These findings identified EVs from long COVID patients as potential mediators of endothelial dysfunction particularly under malnutrition-related conditions. (AU)

• Processo FAPESP: 24/01682-2 - Caracterização das vesículas extracelulares circulantes de pacientes com câncer colorretal.
• Beneficiário: Lígia de Moraes Antunes Corrêa
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 23/10663-9 - Efeito das micropartículas circulantes de pacientes pós-COVID-19 na função endotelial: impacto da restrição proteica
• Beneficiário: Natália Ribeiro Cabacinha Nóbrega
• Modalidade de apoio: Bolsas no Brasil - Programa Fixação de Jovens Doutores
• Processo FAPESP: 13/07607-8 - CMPO - Centro Multidisciplinar de Pesquisa em Obesidade e Doenças Associadas
• Beneficiário: Licio Augusto Velloso
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 20/09799-5 - Caracterização e efeito endotelial das micropartículas circulantes de pacientes com COVID-19: efeito da inibição da bradicinina
• Beneficiário: Ana Paula Couto Davel
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 22/14898-8 - Resposta De Células Endoteliais In Vitro À Presença De Micropartículas Isoladas De Pacientes Pós-Covid-19 Grave
• Beneficiário: Juliana Quinholi Rocha
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 23/01329-8 - Efeito das micropartículas circulantes de pacientes pós-COVID-19 na função endotelial: impacto da restrição proteica
• Beneficiário: Ana Paula Couto Davel
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/26080-4 - Caracterização dos mecanismos moleculares e funcionais envolvidos nas disfunções endócrino-metabólicas, cardiovasculares e neurais induzidas pela restrição de aminoácidos in vitro e in vivo: possível papel terapêutico do ácido biliar TUDCA
• Beneficiário: Everardo Magalhães Carneiro
• Modalidade de apoio: Auxílio à Pesquisa - Temático