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. 2023 Jun 26;2(7):656-672.
doi: 10.1038/s44161-023-00295-x.

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

Lea Dib #  1 , Lada A Koneva #  1 , Andreas Edsfeldt  2   3   4 , Yasemin-Xiomara Zurke  1 , Jiangming Sun  2 , Mihaela Nitulescu  2 , Moustafa Attar  1 , Esther Lutgens  5 , Steffen Schmidt  6 , Marie W Lindholm  6 , Robin P Choudhury  7 , Ismail Cassimjee  1   8 , Regent Lee  8 , Ashok Handa  8 , Isabel Goncalves  2   3 , Stephen N Sansom #  1 , Claudia Monaco #  1
Affiliations
Free PMC article

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

Lea Dib et al. Nat Cardiovasc Res. .
Free PMC article

Erratum in

Abstract

The immune system is integral to cardiovascular health and disease. Targeting inflammation ameliorates adverse cardiovascular outcomes. Atherosclerosis, a major underlying cause of cardiovascular disease (CVD), is conceptualised as a lipid-driven inflammation where macrophages play a non-redundant 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 scRNASeq of human surgical carotid endarterectomies in a discovery cohort with bulk RNASeq and immunohistochemistry in a validation cohort (the Carotid Plaque Imaging Project-CPIP), we reveal the existence of PLIN2hi/TREM1hi macrophages as a toll-like receptor-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 CVD.

Keywords: Atherosclerosis; Cardiovascular Disease; Inflammation; Lipid-associated macrophages; Mechanisms.

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Conflict of interest statement

Competing Interests Statement All authors report no conflict of interest. A.E has received consultancy fees from and/or served on the advisory boards of Novo Nordisk, Sanofi and Amgen but this has not had any relationship with the current study or affected the design/outcome of the study. The remaining authors have no conflicts of interest.

Comment in

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