Macrophage profiling in atherosclerosis: understanding the unstable plaque

IF 7.5 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
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Abstract

The development and rupture of atherosclerotic plaques is a major contributor to myocardial infarctions and ischemic strokes. The dynamic evolution of the plaque is largely attributed to monocyte/macrophage functions, which respond to various stimuli in the plaque microenvironment. To this end, macrophages play a central role in atherosclerotic lesions through the uptake of oxidized low-density lipoprotein that gets trapped in the artery wall, and the induction of an inflammatory response that can differentially affect the stability of the plaque in men and women. In this environment, macrophages can polarize towards pro-inflammatory M1 or anti-inflammatory M2 phenotypes, which represent the extremes of the polarization spectrum that include Mhem, M(Hb), Mox, and M4 populations. However, this traditional macrophage model paradigm has been redefined to include numerous immune and nonimmune cell clusters based on in-depth unbiased single-cell approaches. The goal of this review is to highlight (1) the phenotypic and functional properties of monocyte subsets in the circulation, and macrophage populations in atherosclerotic plaques, as well as their contribution towards stable or unstable phenotypes in men and women, and (2) single-cell RNA sequencing studies that have advanced our knowledge of immune, particularly macrophage signatures present in the atherosclerotic niche. We discuss the importance of performing high-dimensional approaches to facilitate the development of novel sex-specific immunotherapies that aim to reduce the risk of cardiovascular events.

动脉粥样硬化中的巨噬细胞分析:了解不稳定斑块
摘要 动脉粥样硬化斑块的发展和破裂是心肌梗死和缺血性中风的主要诱因。斑块的动态演变在很大程度上归因于单核细胞/巨噬细胞的功能,它们对斑块微环境中的各种刺激做出反应。为此,巨噬细胞在动脉粥样硬化病变中发挥着核心作用,它们吸收被困在动脉壁上的氧化低密度脂蛋白,并诱发炎症反应,从而对男性和女性斑块的稳定性产生不同的影响。在这种环境下,巨噬细胞可极化为促炎的 M1 或抗炎的 M2 表型,它们代表了极化谱的极端,包括 Mhem、M(Hb)、Mox 和 M4 群体。然而,这种传统的巨噬细胞模型范式已被重新定义,以包括基于深入的无偏见单细胞方法的众多免疫和非免疫细胞群。本综述旨在强调:(1)血液循环中单核细胞亚群和动脉粥样硬化斑块中巨噬细胞群的表型和功能特性,以及它们对男性和女性稳定或不稳定表型的贡献;(2)单细胞 RNA 测序研究增进了我们对动脉粥样硬化龛位中存在的免疫,尤其是巨噬细胞特征的了解。我们讨论了采用高维方法的重要性,以促进旨在降低心血管事件风险的新型性别特异性免疫疗法的开发。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Basic Research in Cardiology
Basic Research in Cardiology 医学-心血管系统
CiteScore
16.30
自引率
5.30%
发文量
54
审稿时长
6-12 weeks
期刊介绍: Basic Research in Cardiology is an international journal for cardiovascular research. It provides a forum for original and review articles related to experimental cardiology that meet its stringent scientific standards. Basic Research in Cardiology regularly receives articles from the fields of - Molecular and Cellular Biology - Biochemistry - Biophysics - Pharmacology - Physiology and Pathology - Clinical Cardiology
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