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Macrophage profiling in atherosclerosis: understanding the unstable plaque

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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.

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Funding

This work was supported by the Canadian Institutes of Health Research [PJT-148966, SVB- 145589]; and the Heart & Stroke Foundation of Canada [G-17–0018755]. SSD is a Senior Clinician-Scientist supported by a Fonds de Recherche du Québec-Santé Senior Salary Award.

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  1. Division of Experimental Medicine, Department of Medicine, Faculty of Medicine and Health Sciences, Research Institute of the McGill University Health Centre, McGill University, Montreal, Canada

    Ioanna Gianopoulos & Stella S. Daskalopoulou

  2. Division of Internal Medicine, Department of Medicine, Faculty of Medicine and Health Sciences, McGill University Health Centre, McGill University, Montreal, Canada

    Stella S. Daskalopoulou

  3. Department of Medicine, Research Institute of the McGill University Health Centre, Glen Site, 1001 Decarie Boulevard, EM1.2210, Montreal, Quebec, H4A 3J1, Canada

    Stella S. Daskalopoulou

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Gianopoulos, I., Daskalopoulou, S.S. Macrophage profiling in atherosclerosis: understanding the unstable plaque. Basic Res Cardiol 119, 35–56 (2024). https://doi.org/10.1007/s00395-023-01023-z

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