作者
Joshua Slysz,Arjun Sinha,Matthew DeBerge,Shalini Singh,Harris Avgousti,I R Lee,Kristofor Glinton,Reina Nagasaka,Prarthana Dalal,Shaina J. Alexandria,Ching Man Wai,Ricardo A. Téllez,Mariavittoria Vescovo,Ashwin Sunderraj,Xinkun Wang,Matthew J. Schipma,Ryan Sisk,Rishab Gulati,Jenifer Vallejo,Ryosuke Saigusa,Donald M. Lloyd‐Jones,Jon W. Lomasney,Samuel E. Weinberg,Karen J. Ho,Klaus Ley,Chiara Giannarelli,Edward B. Thorp,Matthew J. Feinstein
摘要
Rationale: 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. Objectives: We investigated intraplaque leukocyte phenotypes and transcriptional polarization in 49 total patients undergoing femoral (N=23) or carotid (N=26) endarterectomy using single-cell ribonucleic acid sequencing (scRNA-seq; N=13), flow cytometry (N=24), and immunohistochemistry (N=12). Findings: Comparative scRNA-seq of CD45 positive-selected leukocytes from femoral (N=9; 35265 cells) and carotid (N=4; 30655 cells) plaque revealed distinct transcriptional profiles. Inflammatory foam cell-like macrophages and monocytes comprised 2.5- to 4-fold higher proportions of myeloid cells in carotid plaques, whereas non-inflammatory foam cell-like macrophages and LYVE1-overexpressing resident-like macrophages comprised 3.5- to 9-fold higher proportions of myeloid cells in femoral plaque (p<0.001 for all). A significant comparative excess of CCR2+ macrophages in carotid versus femoral plaque was observed by flow cytometry in a separate validation cohort. B cells were more prevalent and exhibited a comparatively anti-inflammatory profile in femoral plaque, whereas cytotoxic CD8+ T cells were more prevalent in carotid plaque. Conclusion: Human femoral plaques exhibit distinct macrophage profiles and diminished CD8+ T cell populations compared with carotid plaques. Experimental models elucidating determinants of plaque site-specific cell polarization cues are warranted.