ZFIN Image: Tapia et al., 2025, Fig. 6.

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Fig. 6.

25HC remodels cholesterol metabolism and function of brain endothelial cells. (1) CH25H upregulation was detected in SARS-CoV-2-associated ICH in zebrafish and human foetal brain tissue, as well as in hCMEC/D3 cells exposed to antiviral stimuli [poly(I:C) and IFNβ]. (2) 25HC treatment induced the downregulation of cholesterol synthesis enzymes at both mRNA and protein levels. In zebrafish and hCMEC/D3 cells, this downregulation had an additive effect when combined with pharmacological inhibition of HMGCR by ATV, leading to brain vessel rupture (ICH) in zebrafish and decreased barrier function and cell migration in hCMEC/D3 cells. (3) 25HC treatment in hCMEC/D3 cells also increased cholesterol efflux, which was associated with upregulation of ABCG1. (4) Internalisation of cholesterol into lipid droplets was not observed in 25HC-treated hCMEC/D3 cells. (5) The changes in cholesterol synthesis and efflux in hCMEC/D3 cells were associated with the depletion of plasma membrane-accessible cholesterol. (6) Cholesterol supplementation rescued the levels of accessible cholesterol and mitigated the decrease in barrier function and cell migration induced by 25HC in hCMEC/D3 cells.

Acknowledgments

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