Journal article
Lipid-associated macrophages transition to an inflammatory state in human atherosclerosis, increasing the risk of cerebrovascular complications
- 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, 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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Corrected version of record, pdf, 16.4MB, Terms of use)
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- Publisher copy:
- 10.1038/s44161-023-00295-x
Authors
- Publisher:
- Springer Nature
- Journal:
- Nature Cardiovascular Research More from this journal
- Volume:
- 2
- Issue:
- 7
- Pages:
- 656-672
- Publication date:
- 2023-06-26
- Acceptance date:
- 2023-05-31
- DOI:
- EISSN:
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2731-0590
- Language:
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English
- Keywords:
- Pubs id:
-
1488856
- Local pid:
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pubs:1488856
- Deposit date:
-
2023-07-10
- ARK identifier:
Terms of use
- Copyright holder:
- Dib et al.
- Copyright date:
- 2023
- Rights statement:
- © The Author(s) 2023, corrected publication 2023. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
- Notes:
-
An author correction to this article is available online from Springer Nature at: https://doi.org/10.1038/s44161-023-00328-5
A publisher correction to this article is available online from Springer Nature at: https://doi.org/10.1038/s44161-023-00319-6
- Licence:
- CC Attribution (CC BY)
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