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

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 under...

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Detalles Bibliográficos
Autores principales: Slysz, Joshua, Sinha, Arjun, DeBerge, Matthew, Singh, Shalini, Avgousti, Harris, Lee, Inhyeok, Glinton, Kristofor, Nagasaka, Reina, Dalal, Prarthana, Alexandria, Shaina, Wai, Ching Man, Tellez, Ricardo, Vescovo, Mariavittoria, Sunderraj, Ashwin, Wang, Xinkun, Schipma, Matthew, Sisk, Ryan, Gulati, Rishab, Vallejo, Jenifer, Saigusa, Ryosuke, Lloyd-Jones, Donald M., Lomasney, Jon, Weinberg, Samuel, Ho, Karen, Ley, Klaus, Giannarelli, Chiara, Thorp, Edward B., Feinstein, Matthew J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10544225/
https://www.ncbi.nlm.nih.gov/pubmed/37471165
http://dx.doi.org/10.1172/jci.insight.171359
Descripción
Sumario: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