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  • Dib, LeaUniversity of Oxford (author)

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

  • Article/chapterEnglish2023

Publisher, publication year, extent ...

  • 2023

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:5e115992-c042-4cad-a118-6c77a4769730
  • https://lup.lub.lu.se/record/5e115992-c042-4cad-a118-6c77a4769730URI
  • https://doi.org/10.1038/s44161-023-00295-xDOI

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  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • 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.

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  • Koneva, Lada A.University of Oxford (author)
  • Edsfeldt, AndreasLund University,Lunds universitet,Kardiovaskulär forskning - translationella studier,Forskargrupper vid Lunds universitet,Cardiovascular Research - Translational Studies,Lund University Research Groups,Skåne University Hospital(Swepub:lu)med-aet (author)
  • Zurke, Yasemin XiomaraUniversity of Oxford (author)
  • Sun, JiangmingLund University,Lunds universitet,Kardiovaskulär forskning - translationella studier,Forskargrupper vid Lunds universitet,Cardiovascular Research - Translational Studies,Lund University Research Groups(Swepub:lu)med-js5 (author)
  • Nitulescu, MihaelaLund University,Lunds universitet,Kardiovaskulär forskning - translationella studier,Forskargrupper vid Lunds universitet,Cardiovascular Research - Translational Studies,Lund University Research Groups(Swepub:lu)medf-mni (author)
  • Attar, MoustafaUniversity of Oxford (author)
  • Lutgens, EstherMayo Clinic Minnesota (author)
  • Schmidt, SteffenRoche Innovation Center Copenhagen (author)
  • Lindholm, Marie W.Roche Innovation Center Copenhagen(Swepub:lu)medf-mli (author)
  • Choudhury, Robin P.University of Oxford (author)
  • Cassimjee, IsmailUniversity of Oxford (author)
  • Lee, RegentUniversity of Oxford (author)
  • Handa, AshokUniversity of Oxford (author)
  • Goncalves, IsabelLund University,Lunds universitet,Kardiovaskulär forskning - translationella studier,Forskargrupper vid Lunds universitet,Cardiovascular Research - Translational Studies,Lund University Research Groups,Skåne University Hospital(Swepub:lu)medf-igo (author)
  • Sansom, Stephen N.University of Oxford (author)
  • Monaco, ClaudiaUniversity of Oxford (author)
  • University of OxfordKardiovaskulär forskning - translationella studier (creator_code:org_t)

Related titles

  • In:Nature Cardiovascular Research2:7, s. 656-6722731-0590

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