학술논문
Single-cell profiling reveals inflammatory polarization of human carotid versus femoral plaque leukocytes
Document Type
article
Author
Joshua Slysz; Arjun Sinha; Matthew DeBerge; Shalini Singh; Harris Avgousti; Inhyeok Lee; Kristofor Glinton; Reina Nagasaka; Prarthana Dalal; Shaina Alexandria; Ching Man Wai; Ricardo Tellez; Mariavittoria Vescovo; Ashwin Sunderraj; Xinkun Wang; Matthew Schipma; Ryan Sisk; Rishab Gulati; Jenifer Vallejo; Ryosuke Saigusa; Donald M. Lloyd-Jones; Jon Lomasney; Samuel Weinberg; Karen Ho; Klaus Ley; Chiara Giannarelli; Edward B. Thorp; Matthew J. Feinstein
Source
JCI Insight, Vol 8, Iss 17 (2023)
Subject
Language
English
ISSN
2379-3708
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