Lipid-associated macrophages transition to an inflammatory state in human atherosclerosis increasing the risk of cerebrovascular complications.
Nat Cardiovasc Res
; 2(7): 656-672, 2023 Jun 26.
Article
en En
| MEDLINE
| ID: mdl-38362263
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Tipo de estudio:
Etiology_studies
/
Risk_factors_studies
Idioma:
En
Revista:
Nat Cardiovasc Res
Año:
2023
Tipo del documento:
Article