TY - JOUR
AU - Passi, Rainha
AU - Cholewa-Waclaw, Justyna
AU - Wereski, Ryan
AU - Bennett, Matthew
AU - Veizades, Stefan
AU - Berkeley, Bronwyn
AU - Caporali, Andrea
AU - Li, Ziwen
AU - Rodor, Julie
AU - Dewerchin, Mieke
AU - Mills, Nicholas L.
AU - Beqqali, Abdelaziz
AU - Brittan, Mairi
AU - Baker, Andrew H.
PY - 2024
DA - January
TI - COVID-19 plasma induces subcellular remodelling within the pulmonary microvascular endothelium
JO - Vascular Pharmacology
VL - 154
DO - https://doi.org/10.1016/j.vph.2024.107277
AB - Background COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect multiple organ systems, including the pulmonary vasculature. Endothelial cells (ECs) are thought to play a key role in the propagation of COVID-19, however, our understanding of the exact scale of dysregulation sustained by the pulmonary microvasculature (pMV) remains incomplete. Here we aim to identify transcriptional, phenotypic, and functional changes within the pMV induced by COVID-19. Methods and results Human pulmonary microvascular endothelial cells (HPMVEC) treated with plasma acquired from patients hospitalised with severe COVID-19 were compared to HPMVEC treated with plasma from patients hospitalised without COVID-19 but with other severe illnesses. Exposure to COVID-19 plasma caused a significant functional decline in HPMVECs as seen by a decrease in both cell viability via the WST-1 cell-proliferation assay and cell-to-cell barrier function as measured by electric cell-substrate impedance sensing. High-content imaging using a Cell Painting image-based assay further quantified morphological variations within sub-cellular organelles to show phenotypic changes in the whole endothelial cell, nucleus, mitochondria, plasma membrane and nucleolus morphology. RNA-sequencing of HPMVECs treated with COVID-19 plasma suggests the observed phenotype may, in part, be regulated by genes such as SMAD7, BCOR, SFMBT1, IFIT5 and ZNF566 which are involved in transcriptional regulation, protein monoubiquitination and TGF-β signalling. Conclusion and impact During COVID-19, the pMV undergoes significant remodelling, which is evident based on the functional, phenotypic, and transcriptional changes seen following exposure to COVID-19 plasma. The observed morphological variation may be responsible for downstream complications, such as a decline in overall cellular function and cell-to-cell barrier integrity. Moreover, genes identified through bulk RNA sequencing may contribute to our understanding of the observed phenotype and assist in developing strategies that can inform the rescue of the dysregulated endothelium.
PB - Elsevier
UR - https://www.research.ed.ac.uk/en/publications/7467c468-3505-4f79-87ca-bf0e0678d85a
KW - Coronavirus (COVID-19)
ER