Protein C Pretreatment Protects Endothelial Cells from SARS-CoV-2-Induced Activation

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Silva, Bruna Rafaela dos Santos ; Sidarta-Oliveira, Davi ; Morari, Joseane ; Bombassaro, Bruna ; Jara, Carlos Poblete ; Simeoni, Camila Lopes ; Parise, Pierina Lorencini ; Proenca-Modena, Jose Luiz ; Velloso, Licio A. ; Velander, William H. ; Araujo, Eliana P.

• Tipo de documento: Artigo Científico
• Fonte: Viruses-Basel; v. 16, n. 7, p. 17-pg., 2024-07-01.

Resumo

SARS-CoV-2 can induce vascular dysfunction and thrombotic events in patients with severe COVID-19; however, the cellular and molecular mechanisms behind these effects remain largely unknown. In this study, we used a combination of experimental and in silico approaches to investigate the role of PC in vascular and thrombotic events in COVID-19. Single-cell RNA-sequencing data from patients with COVID-19 and healthy subjects were obtained from the publicly available Gene Expression Omnibus (GEO) repository. In addition, HUVECs were treated with inactive protein C before exposure to SARS-CoV-2 infection or a severe COVID-19 serum. An RT-qPCR array containing 84 related genes was used, and the candidate genes obtained were evaluated. Activated protein C levels were measured using an ELISA kit. We identified at the single-cell level the expression of several pro-inflammatory and pro-coagulation genes in endothelial cells from the patients with COVID-19. Furthermore, we demonstrated that exposure to SARS-CoV-2 promoted transcriptional changes in HUVECs that were partly reversed by the activated protein C pretreatment. We also observed that the serum of severe COVID-19 had a significant amount of activated protein C that could protect endothelial cells from serum-induced activation. In conclusion, activated protein C protects endothelial cells from pro-inflammatory and pro-coagulant effects during exposure to the SARS-CoV-2 virus. (AU)

• Processo FAPESP: 20/04558-0 - Caracterização de fatores de risco intrínsecos e o desenvolvimento de novas alternativas de diagnóstico e tratamento para COVID-19
• Beneficiário: José Luiz Proença Módena
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• 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