[HTML][HTML] Single-cell transcriptome profiles reveal fibrocytes as potential targets of cell therapies for abdominal aortic aneurysm

B Li, X Song, W Guo, Y Hou, H Hu, W Ge… - Frontiers in …, 2021 - frontiersin.org
B Li, X Song, W Guo, Y Hou, H Hu, W Ge, T Fan, Z Han, Z Li, P Yang, R Gao, H Zhao…
Frontiers in Cardiovascular Medicine, 2021frontiersin.org
Abdominal aortic aneurysm (AAA) is potentially life-threatening in aging population due to
the risk of aortic rupture and a lack of optimal treatment. The roles of different vascular and
immune cells in AAA formation and pathogenesis remain to be future characterized. Single-
cell RNA sequencing was performed on an angiotensin (Ang) II-induced mouse model of
AAA. Macrophages, B cells, T cells, fibroblasts, smooth muscle cells and endothelial cells
were identified through bioinformatic analyses. The discovery of multiple subtypes of …
Abdominal aortic aneurysm (AAA) is potentially life-threatening in aging population due to the risk of aortic rupture and a lack of optimal treatment. The roles of different vascular and immune cells in AAA formation and pathogenesis remain to be future characterized. Single-cell RNA sequencing was performed on an angiotensin (Ang) II-induced mouse model of AAA. Macrophages, B cells, T cells, fibroblasts, smooth muscle cells and endothelial cells were identified through bioinformatic analyses. The discovery of multiple subtypes of macrophages, such as the re-polarization of Trem2+Acp5+ osteoclast-like and M2-like macrophages toward the M1 type macrophages, indicates the heterogenous nature of macrophages during AAA development. More interestingly, we defined CD45+COL1+ fibrocytes, which was further validated by flow cytometry and immunostaining in mouse and human AAA tissues. We then reconstituted these fibrocytes into mice with Ang II-induced AAA and found the recruitment of these fibrocytes in mouse AAA. More importantly, the fibrocyte treatment exhibited a protective effect against AAA development, perhaps through modulating extracellular matrix production and thus enhancing aortic stability. Our study reveals the heterogeneity of macrophages and the involvement of a novel cell type, fibrocyte, in AAA. Fibrocyte may represent a potential cell therapy target for AAA.
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