Department of Life Science, Research Institute for Natural Sciences, Hanyang Institute of Bioscience and Biotechnology, College of Natural Sciences, Hanyang University, Seoul, Republic of Korea.
Curr Opin Lipidol. 2022 Oct 1;33(5):283-288. doi: 10.1097/MOL.0000000000000842. Epub 2022 Aug 3.
Recent findings from single-cell transcriptomic studies prompted us to revisit the role of plaque foamy macrophages in the pathogenesis of atherosclerosis. In this review, we compared the gene expression profile of plaque foamy macrophages with those of other disease-associated macrophages and discussed their functions in the pathogenesis of atherosclerosis.
To understand the phenotypes of macrophages in atherosclerotic aorta, many research groups performed single-cell RNA sequencing analysis and found that there are distinct phenotypic differences among intimal foamy, nonfoamy and adventitial macrophages. Especially, the plaque foamy macrophages express triggering receptor expressed on myeloid cells 2 (TREM2), a key common feature of disease-associated macrophages in Alzheimer's disease, obesity, cirrhosis and nonalcoholic steatohepatitis. These TREM2 + macrophages seem to be protective against chronic inflammation.
As the gene expression profile of plaque foamy macrophages is highly comparable to that of lipid-associated macrophages from obesity, we named the plaque foamy macrophages as plaque lipid-associated macrophages (PLAMs). PLAMs have a high level of gene expression related to phago/endocytosis, lysosome, lipid metabolism and oxidative phosphorylation. Considering the protective function of lipid-associated macrophages against adipose tissue inflammation, PLAMs may suppress atherosclerotic inflammation by removing modified lipids and cell debris in the plaque.
单细胞转录组学研究的新发现促使我们重新审视斑块泡沫巨噬细胞在动脉粥样硬化发病机制中的作用。在这篇综述中，我们将斑块泡沫巨噬细胞的基因表达谱与其他与疾病相关的巨噬细胞进行了比较，并讨论了它们在动脉粥样硬化发病机制中的作用。
为了了解动脉粥样硬化主动脉中巨噬细胞的表型，许多研究小组进行了单细胞 RNA 测序分析，发现内膜泡沫、非泡沫和外膜巨噬细胞之间存在明显的表型差异。特别是，斑块泡沫巨噬细胞表达髓样细胞触发受体 2（TREM2），这是阿尔茨海默病、肥胖症、肝硬化和非酒精性脂肪性肝炎等与疾病相关的巨噬细胞的一个关键共同特征。这些 TREM2+巨噬细胞似乎对慢性炎症有保护作用。
由于斑块泡沫巨噬细胞的基因表达谱与肥胖相关的脂质相关巨噬细胞高度相似，我们将斑块泡沫巨噬细胞命名为斑块脂质相关巨噬细胞（PLAMs）。PLAMs 具有高水平的与吞噬/内吞作用、溶酶体、脂质代谢和氧化磷酸化相关的基因表达。考虑到脂质相关巨噬细胞对脂肪组织炎症的保护作用，PLAMs 可能通过清除斑块中修饰的脂质和细胞碎片来抑制动脉粥样硬化炎症。
