Gui Yuzhou, Zheng Hongchao, Cao Richard Y
Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China.
Shanghai Engineering Research Center of Phase I Clinical Research and Quality Consistency Evaluation for Drugs, Shanghai, China.
Front Cardiovasc Med. 2022 Apr 13;9:845942. doi: 10.3389/fcvm.2022.845942. eCollection 2022.
Foam cells play a vital role in the initiation and development of atherosclerosis. This review aims to summarize the novel insights into the origins, consequences, and molecular mechanisms of foam cells in atherosclerotic plaques. Foam cells are originated from monocytes as well as from vascular smooth muscle cells (VSMC), stem/progenitor cells, and endothelium cells. Novel technologies including lineage tracing and single-cell RNA sequencing (scRNA-seq) have revolutionized our understanding of subtypes of monocyte- and VSMC-derived foam cells. By using scRNA-seq, three main clusters including resident-like, inflammatory, and triggering receptor expressed on myeloid cells-2 (Trem2 ) are identified as the major subtypes of monocyte-derived foam cells in atherosclerotic plaques. Foam cells undergo diverse pathways of programmed cell death including apoptosis, autophagy, necroptosis, and pyroptosis, contributing to the necrotic cores of atherosclerotic plaques. The formation of foam cells is affected by cholesterol uptake, efflux, and esterification. Novel mechanisms including nuclear receptors, non-coding RNAs, and gut microbiota have been discovered and investigated. Although the heterogeneity of monocytes and the complexity of non-coding RNAs make obstacles for targeting foam cells, further in-depth research and therapeutic exploration are needed for the better management of atherosclerosis.
泡沫细胞在动脉粥样硬化的发生和发展中起着至关重要的作用。本综述旨在总结对动脉粥样硬化斑块中泡沫细胞的起源、后果及分子机制的新见解。泡沫细胞起源于单核细胞以及血管平滑肌细胞（VSMC）、干/祖细胞和内皮细胞。包括谱系追踪和单细胞RNA测序（scRNA-seq）在内的新技术彻底改变了我们对单核细胞和VSMC衍生的泡沫细胞亚型的理解。通过使用scRNA-seq，在动脉粥样硬化斑块中，包括驻留样、炎症性和髓系细胞触发受体2（Trem2）在内的三个主要簇被确定为单核细胞衍生的泡沫细胞的主要亚型。泡沫细胞经历多种程序性细胞死亡途径，包括凋亡、自噬、坏死性凋亡和焦亡，这有助于动脉粥样硬化斑块坏死核心的形成。泡沫细胞的形成受胆固醇摄取、流出和酯化的影响。已发现并研究了包括核受体、非编码RNA和肠道微生物群在内的新机制。尽管单核细胞的异质性和非编码RNA的复杂性给靶向泡沫细胞带来了障碍，但为了更好地管理动脉粥样硬化，仍需要进一步深入研究和进行治疗探索。
