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COVID-19 plasma induces subcellular remodelling within the pulmonary microvascular endothelium.
Passi, Rainha; Cholewa-Waclaw, Justyna; Wereski, Ryan; Bennett, Matthew; Veizades, Stefan; Berkeley, Bronwyn; Caporali, Andrea; Li, Ziwen; Rodor, Julie; Dewerchin, Mieke; Mills, Nicholas L; Beqqali, Abdelaziz; Brittan, Mairi; Baker, Andrew H.
Affiliation
  • Passi R; BHF Centre for Cardiovascular Science, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, and VIB Centre for Cancer Biology, VIB, Leuven, Belgium.
  • Cholewa-Waclaw J; Centre for Regenerative Medicine, Institute for Regeneration and Repair, Edinburgh Bioquarter, University of Edinburgh, 5 Little France Drive, Edinburgh EH16 4UU, UK.
  • Wereski R; BHF Centre for Cardiovascular Science, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
  • Bennett M; BHF Centre for Cardiovascular Science, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
  • Veizades S; BHF Centre for Cardiovascular Science, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK; Stanford Cardiovascular Institute, Stanford University, Stanford 94305, CA, USA.
  • Berkeley B; BHF Centre for Cardiovascular Science, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
  • Caporali A; BHF Centre for Cardiovascular Science, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
  • Li Z; BHF Centre for Cardiovascular Science, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
  • Rodor J; BHF Centre for Cardiovascular Science, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
  • Dewerchin M; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, and VIB Centre for Cancer Biology, VIB, Leuven, Belgium.
  • Mills NL; BHF Centre for Cardiovascular Science, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
  • Beqqali A; BHF Centre for Cardiovascular Science, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
  • Brittan M; BHF Centre for Cardiovascular Science, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
  • Baker AH; BHF Centre for Cardiovascular Science, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK; Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, 6229 HX Maastricht, the Netherlands. Electronic address: andy.baker@ed.ac.uk.
Vascul Pharmacol ; 154: 107277, 2024 03.
Article in En | MEDLINE | ID: mdl-38266794
ABSTRACT

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-ß 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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Endothelial Cells / COVID-19 Limits: Humans Language: En Journal: Vascul Pharmacol Journal subject: ANGIOLOGIA / FARMACOLOGIA Year: 2024 Document type: Article Affiliation country: Belgium Country of publication: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Endothelial Cells / COVID-19 Limits: Humans Language: En Journal: Vascul Pharmacol Journal subject: ANGIOLOGIA / FARMACOLOGIA Year: 2024 Document type: Article Affiliation country: Belgium Country of publication: United States