Lipid-associated macrophages transition to an inflammatory state in human atherosclerosis, increasing the risk of cerebrovascular complications

Dib, L. ORCID: https://orcid.org/0000-0001-5889-4738, Koneva, L. A., Edsfeldt, A., Zurke, Y.-X., Sun, J., Nitulescu, M., Attar, M., Lutgens, E., Schmidt, S., Lindholm, M. W., Choudhury, R. P., Cassimjee, I., Lee, R., Handa, A., Goncalves, I., Sansom, S. N. and Monaco, C. (2023) Lipid-associated macrophages transition to an inflammatory state in human atherosclerosis, increasing the risk of cerebrovascular complications. Nature Cardiovascular Research, 2. pp. 656-672. ISSN 2731-0590 doi: 10.1038/s44161-023-00295-x

Abstract/Summary

The immune system is integral to cardiovascular health and disease. Targeting inflammation ameliorates adverse cardiovascular outcomes. Atherosclerosis, a major underlying cause of cardiovascular disease, is conceptualized as lipid-driven inflammation in which macrophages play a nonredundant role. However, evidence emerging so far from single-cell atlases suggests a dichotomy between lipid-associated and inflammatory macrophage states. Here, we present an inclusive reference atlas of human intraplaque immune cell communities. Combining single-cell RNA sequencing (scRNA-seq) of human surgical carotid endarterectomies in a discovery cohort with bulk RNA-seq and immunohistochemistry in a validation cohort (the Carotid Plaque Imaging Project), we reveal the existence of PLIN2hi/TREM1hi macrophages as a Toll-like receptor (TLR)- dependent inflammatory lipid-associated macrophage state linked to cerebrovascular events. Our study shifts the current paradigm of lipid-driven inflammation by providing biological evidence for a pathogenic macrophage transition to an inflammatory lipid-associated phenotype and for its targeting as a new treatment strategy for cardiovascular disease.

Item Type	Article
URI	https://centaur.reading.ac.uk/id/eprint/123188
Identification Number/DOI	10.1038/s44161-023-00295-x
Refereed	Yes
Divisions	Life Sciences > School of Biological Sciences > Biomedical Sciences
Publisher	Springer
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