CXCL10-dependent epithelial-vascular cross-talk for endothelial activation following SARS-CoV-2 infection.

Publication date: Jul 01, 2025

The blood vessel network is heavily impacted by SARS-CoV-2 infection. How SARS-CoV-2 contributes to vascular inflammation and whether epithelio-endothelial cross-talk is involved remain unclear. We investigated in detail the interaction between SARS-CoV-2 and the vasculature using 2D and 3D vesseloid in vitro models. We first assessed whether SARS-CoV-2 is able to directly infect endothelial cells. In the absence of ACE2 in endothelial cells, no productive infection was detected. Low uptake of viral particles by ACE2-overexpressing endothelial cells was observed without efficient viral production. Thus, the indirect effect of SARS-CoV-2 infection may involve epithelio-endothelial cell cross-talk. After infection of the epithelial cells, a significant inflammatory response was detected in the endothelial cells. CXCL10 was the most highly expressed proinflammatory cytokine involved in this intercellular communication, and its function was subsequently explored. Finally, the clinical relevance of our findings was confirmed in two patient cohorts.

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Concepts Keywords
Cxcl10 ACE2 protein, human
Efficient Angiotensin-Converting Enzyme 2
Endothelial Angiotensin-Converting Enzyme 2
Models Cell Communication
Viral Chemokine CXCL10
Chemokine CXCL10
Chemokines
COVID-19
CXCL10
CXCL10 protein, human
Endothelial Cells
Endothelium
Endothelium, Vascular
Epithelial Cells
Humans
SARS-CoV-2
SARS-CoV-2

Semantics

Type Source Name
disease MESH SARS-CoV-2 infection
pathway REACTOME SARS-CoV-2 Infection
disease MESH inflammation
disease MESH infection
disease IDO production
disease IDO cell
disease MESH clinical relevance
disease MESH severe acute respiratory syndrome
disease MESH cytokine storm
disease MESH syndrome
disease MESH edema
disease IDO facility
drug DRUGBANK Coenzyme M
disease IDO blood
disease IDO protein
disease MESH viral infection
pathway KEGG Viral replication
disease MESH death
disease IDO replication

Original Article

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