1. Human Brain Microvascular Endothelial Cells Exposure to SARS-CoV-2 Leads to Inflammatory Activation through NF-κB Non-Canonical Pathway and Mitochondrial Remodeling
- Author
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Carolline Soares Motta, Silvia Torices, Barbara Gomes da Rosa, Anne Caroline Marcos, Liandra Alvarez-Rosa, Michele Siqueira, Thaidy Moreno-Rodriguez, Aline da Rocha Matos, Braulia Costa Caetano, Jessica Santa Cruz de Carvalho Martins, Luis Gladulich, Erick Loiola, Olivia R. M. Bagshaw, Jeffrey A. Stuart, Marilda M. Siqueira, Joice Stipursky, Michal Toborek, and Daniel Adesse
- Subjects
COVID-19 ,blood–brain barrier ,mitochondrial dynamics ,NF-κB signaling pathway ,endothelial activation ,Microbiology ,QR1-502 - Abstract
Neurological effects of COVID-19 and long-COVID-19, as well as neuroinvasion by SARS-CoV-2, still pose several questions and are of both clinical and scientific relevance. We described the cellular and molecular effects of the human brain microvascular endothelial cells (HBMECs) in vitro exposure by SARS-CoV-2 to understand the underlying mechanisms of viral transmigration through the blood–brain barrier. Despite the low to non-productive viral replication, SARS-CoV-2-exposed cultures displayed increased immunoreactivity for cleaved caspase-3, an indicator of apoptotic cell death, tight junction protein expression, and immunolocalization. Transcriptomic profiling of SARS-CoV-2-challenged cultures revealed endothelial activation via NF-κB non-canonical pathway, including RELB overexpression and mitochondrial dysfunction. Additionally, SARS-CoV-2 led to altered secretion of key angiogenic factors and to significant changes in mitochondrial dynamics, with increased mitofusin-2 expression and increased mitochondrial networks. Endothelial activation and remodeling can further contribute to neuroinflammatory processes and lead to further BBB permeability in COVID-19.
- Published
- 2023
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