Cellular Heterogeneity of Activated Primary Human Macrophages and Associated Drug–Gene Networks: From Biology to Precision Therapeutics
Authors' conclusion
We characterized 2 clusters of macrophages in atherosclerosis and combined our cellular data with a cell-signature drug library to identify a novel compound that targets a subset of macrophages in atherosclerosis.
Study context
- Population
- Primary human macrophages activated by IFNγ; murine model of atherosclerosis
- Comparison
- Mi vs Mp
Methodological detailsin vitro, murine model of atherosclerosis
- In vitro
- Murine model of atherosclerosis
Main finding
As reported in the abstract
- scRNA-seq identified 2 major M(IFNγ) clusters: inflammatory (M(IFNγ)i) and phagocytic (M(IFNγ)p)
- M(IFNγ)i: higher inflammatory chemokine expression and amino acid consumption vs M(IFNγ)p
- M(IFNγ)p: more phagocytotic and chemotactic, higher Krebs cycle activity, less glycolysis vs M(IFNγ)i
- Human carotid atherosclerotic plaques contained 2 such macrophage clusters
- LINCS analysis identified BI-2536 as potential compound to decrease M(IFNγ)i
- BI-2536 in vitro decreased inflammatory chemokine expression and secretion, shrinking M(IFNγ)i and expanding M(IFNγ)p
- BI-2536 in vivo shifted macrophage phenotype, modulated inflammation, decreased atherosclerosis and calcification
Original publication
Cellular Heterogeneity of Activated Primary Human Macrophages and Associated Drug–Gene Networks: From Biology to Precision Therapeutics. Circulation. Published 18 October 2023. doi:10.
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