Single-cell profiling reveals inflammatory polarization of human carotid versus femoral plaque leukocytes.

Autor:	Slysz J; Division of Cardiology, Department of Medicine., Sinha A; Division of Cardiology, Department of Medicine., DeBerge M; Department of Pathology, and., Singh S; Division of Cardiology, Department of Medicine., Avgousti H; Division of Cardiology, Department of Medicine., Lee I; Division of Cardiology, Department of Medicine., Glinton K; Division of Cardiology, Department of Medicine.; Department of Pathology, and., Nagasaka R; Division of Cardiology, Department of Medicine., Dalal P; Division of Cardiology, Department of Medicine., Alexandria S; Department of Preventive Medicine at Northwestern University Feinberg School of Medicine (NUFSM), Chicago, Illinois, USA., Wai CM; Northwestern University Sequencing Core, Chicago, Illinois, USA., Tellez R; Division of Cardiology, Department of Medicine.; Department of Pathology, and., Vescovo M; Department of Pathology, and., Sunderraj A; Division of Cardiology, Department of Medicine., Wang X; Northwestern University Sequencing Core, Chicago, Illinois, USA., Schipma M; Northwestern University Sequencing Core, Chicago, Illinois, USA., Sisk R; Division of Cardiology, Department of Medicine., Gulati R; La Jolla Institute of Immunology, La Jolla, California, USA., Vallejo J; La Jolla Institute of Immunology, La Jolla, California, USA., Saigusa R; La Jolla Institute of Immunology, La Jolla, California, USA., Lloyd-Jones DM; Division of Cardiology, Department of Medicine.; Department of Preventive Medicine at Northwestern University Feinberg School of Medicine (NUFSM), Chicago, Illinois, USA., Lomasney J; Department of Pathology, and., Weinberg S; Department of Pathology, and., Ho K; Division of Vascular Surgery, NUFSM, Chicago, Illinois, USA., Ley K; Immunology Center of Georgia, Augusta, Georgia, USA., Giannarelli C; Department of Medicine and.; Department of Pathology, New York University, New York, New York, USA., Thorp EB; Department of Pathology, and., Feinstein MJ; Division of Cardiology, Department of Medicine.; Department of Pathology, and.; Department of Preventive Medicine at Northwestern University Feinberg School of Medicine (NUFSM), Chicago, Illinois, USA.
Jazyk:	angličtina
Zdroj:	JCI insight [JCI Insight] 2023 Sep 08; Vol. 8 (17). Date of Electronic Publication: 2023 Sep 08.
DOI:	10.1172/jci.insight.171359
Abstrakt:	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.
Databáze:	MEDLINE
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