TY - JOUR
T1 - Single-cell profiling reveals inflammatory polarization of human carotid versus femoral plaque leukocytes
AU - Slysz, Joshua
AU - Sinha, Arjun
AU - DeBerge, Matthew
AU - Singh, Shalini
AU - Avgousti, Harris
AU - Lee, Inhyeok
AU - Glinton, Kristofor
AU - Nagasaka, Reina
AU - Dalal, Prarthana
AU - Alexandria, Shaina
AU - Wai, Ching Man
AU - Tellez, Ricardo
AU - Vescovo, Mariavittoria
AU - Sunderraj, Ashwin
AU - Wang, Xinkun
AU - Schipma, Matthew
AU - Sisk, Ryan
AU - Gulati, Rishab
AU - Vallejo, Jenifer
AU - Saigusa, Ryosuke
AU - Lloyd-Jones, Donald M.
AU - Lomasney, Jon
AU - Weinberg, Samuel
AU - Ho, Karen
AU - Ley, Klaus
AU - Giannarelli, Chiara
AU - Thorp, Edward B.
AU - Feinstein, Matthew J.
N1 - Publisher Copyright:
Copyright: © 2023, Slysz et al.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
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U2 - 10.1172/jci.insight.171359
DO - 10.1172/jci.insight.171359
M3 - Article
C2 - 37471165
AN - SCOPUS:85170294835
SN - 2379-3708
VL - 8
JO - JCI Insight
JF - JCI Insight
IS - 17
M1 - e171359
ER -