SARS-CoV-2 Infection Remodels the Phenotype and Promotes Angiogenesis of Primary Human Lung Endothelial Cells

Francesca Caccuri, Antonella Bugatti, Alberto Zani, Antonella De Palma, Dario Di Silvestre, Ekta Manocha, Federica Filippini, Serena Messali, Paola Chiodelli, Giovanni Campisi, Simona Fiorentini, Fabio Facchetti, Pierluigi Mauri, Arnaldo Caruso

Risultato della ricerca: Contributo in rivistaArticolo in rivista

Abstract

SARS-CoV-2-associated acute respiratory distress syndrome (ARDS) and acute lung injury are life-threatening manifestations of severe viral infection. The pathogenic mechanisms that lead to respiratory complications, such as endothelialitis, intussusceptive angiogenesis, and vascular leakage remain unclear. In this study, by using an immunofluorescence assay and in situ RNA-hybridization, we demonstrate the capability of SARS-CoV-2 to infect human primary lung microvascular endothelial cells (HL-mECs) in the absence of cytopathic effects and release of infectious particles. Preliminary data point to the role of integrins in SARS-CoV-2 entry into HL-mECs in the absence of detectable ACE2 expression. Following infection, HL-mECs were found to release a plethora of pro-inflammatory and pro-angiogenic molecules, as assessed by microarray analyses. This conditioned microenvironment stimulated HL-mECs to acquire an angiogenic phenotype. Proteome analysis confirmed a remodeling of SARS-CoV-2-infected HL-mECs to inflammatory and angiogenic responses and highlighted the expression of antiviral molecules as annexin A6 and MX1. These results support the hypothesis of a direct role of SARS-CoV-2-infected HL-mECs in sustaining vascular dysfunction during the early phases of infection. The construction of virus-host interactomes will be instrumental to identify potential therapeutic targets for COVID-19 aimed to inhibit HL-mEC-sustained inflammation and angiogenesis upon SARS-CoV-2 infection.
Lingua originaleEnglish
pagine (da-a)1438-N/A
RivistaMicroorganisms
Volume9
DOI
Stato di pubblicazionePubblicato - 2021

Keywords

  • COVID-19
  • angiogenesis
  • proteome
  • infection
  • endothelial cell dysfunction

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