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Single-cell profiling reveals inflammatory polarization of human carotid versus femoral plaque leukocytes
- Source :
- JCI Insight, Vol 8, Iss 17 (2023)
- Publication Year :
- 2023
- Publisher :
- American Society for Clinical investigation, 2023.
-
Abstract
- Femoral atherosclerotic plaques are less inflammatory than carotid plaques histologically, but limited cell-level data exist regarding comparative immune landscapes and polarization at these sites. We investigated intraplaque leukocyte phenotypes and transcriptional polarization in 49 patients undergoing femoral (n = 23) or carotid (n = 26) endarterectomy using single-cell RNA-Seq (scRNA-Seq; n = 13), flow cytometry (n = 24), and IHC (n = 12). Comparative scRNA-Seq of CD45+-selected leukocytes from femoral (n = 9; 35,265 cells) and carotid (n = 4; 30,655 cells) plaque revealed distinct transcriptional profiles. Inflammatory foam cell–like macrophages and monocytes comprised higher proportions of myeloid cells in carotid plaques, whereas noninflammatory foam cell–like macrophages and LYVE1-overexpressing macrophages comprised higher proportions of myeloid cells in femoral plaque (P < 0.001 for all). A significant comparative excess of CCR2+ macrophages in carotid versus plaque was observed by flow cytometry in a separate validation cohort. B cells were more prevalent and exhibited a comparatively antiinflammatory profile in femoral plaque, whereas cytotoxic CD8+ T cells were more prevalent in carotid plaque. In conclusion, human femoral plaques exhibit distinct macrophage phenotypic and transcriptional profiles as well as diminished CD8+ T cell populations compared with human carotid plaques
- Subjects :
- Cardiology
Inflammation
Medicine
Subjects
Details
- Language :
- English
- ISSN :
- 23793708
- Volume :
- 8
- Issue :
- 17
- Database :
- Directory of Open Access Journals
- Journal :
- JCI Insight
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.787c69545d94017b8a54872a8ab6581
- Document Type :
- article
- Full Text :
- https://doi.org/10.1172/jci.insight.171359