Abstract
Purpose
Macrophages play vital roles in the development of atherosclerosis in responding to lipid accumulation and inflammation. Macrophages were classified as inflammatory (M1) and alternatively activated (M2) macrophage types based on results of in vitro experiments. On the other hand, the composition of macrophages in vivo is more complex and remains unresolved. This review summarizes the transcriptional variations of macrophages in atherosclerosis plaques that were discovered by single-cell RNA sequencing (scRNA-seq) to better understand their contribution to atherosclerosis.
Recent Findings
ScRNA-seq provides a more detailed transcriptional landscape of macrophages in atherosclerosis, which challenges the traditional view. By mining the data of GSE97310, we discovered the transcriptional variations of macrophages in LDLR−/− mice that were fed with high-fat diet (HFD) for 11 and 20 weeks. Cells were represented in a two-dimensional tSNE plane and clusters were identified and annotated via Seurat and SingleR respectively, which were R toolkits for single-cell genomics. The results showed that in healthy conditions, Trem2hi (high expression of triggering receptors expressed on myeloid cells 2)-positive, inflammatory, and resident-like macrophages make up 68%, 18%, and 6% of total macrophages respectively. When mice were fed with HFD for 11 weeks, Trem2hi, monocytes, and monocyte-derived dendritic cells take possession of 40%, 18%, and 17% of total macrophages respectively. After 20 weeks of HFD feeding, Trem2hi, inflammatory, and resident-like macrophages occupied 12%, 37%, and 35% of total macrophages respectively.
Summary
The phenotypes of macrophages are very different from the previous studies. In general, Trem2hi macrophages are the most abundant population in healthy mice, while the proportion of monocytes increases after 11 weeks of HFD. Most importantly, inflammatory and resident-like macrophages make up 70% of the macrophage populations after 20 weeks of HFD. These strongly indicate that inflammatory and resident-like macrophages promote the progression of atherosclerosis plaques.
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Funding
This work was supported by the National Natural Science Foundation of China (81503504, 81573733, 81083615, 81704056). Tianjin Education Commission Research Project (Grant 2019KJ055) and Extension Project of First Teaching Hospital of Tianjin University of Traditional Chinese Medicine (Grant 201911). Natural Science Fund Project in Jiangxi province (20171ACB21075, 20181BAB205073).
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Hao Deng, Yingxin Sun and Wenyun Zeng contributed equally to this work.
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Hao Deng, Yingxin Sun, Wenyun Zeng, Huhu Li, Maojuan Guo, Lin Yang, Bin Lu, Bin Yu, Guanwei Fan, Qing Gao, and Xijuan Jiang declare no conflict of interest.
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Deng, H., Sun, Y., Zeng, W. et al. New Classification of Macrophages in Plaques: a Revolution. Curr Atheroscler Rep 22, 31 (2020). https://doi.org/10.1007/s11883-020-00850-y
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DOI: https://doi.org/10.1007/s11883-020-00850-y