[en] During atherogenesis, plaque macrophages take up and process deposited lipids, trigger inflammation, and form necrotic cores. The traditional inflammatory/anti-inflammatory paradigm has proven insufficient in explaining their complex disease-driving mechanisms. Instead, we now appreciate that macrophages exhibit remarkable heterogeneity and functional specialization in various pathological contexts, including atherosclerosis. Technical advances for studying individual cells, especially single-cell RNA sequencing, indeed allowed to identify novel macrophage subsets in both murine and human atherosclerosis, highlighting the existence of diverse macrophage activation states throughout pathogenesis. In addition, recent studies highlighted the role of the local microenvironment in shaping the macrophages' phenotype and function. However, this remains largely undescribed in the context of atherosclerosis. In this review we explore the origins of macrophages and their functional specialization, shedding light on the diverse sources of macrophage accumulation in the atherosclerotic plaque. Next, we discuss the phenotypic diversity observed in both murine and human atherosclerosis, elucidating their distinct functions and spatial distribution within plaques. Finally, we highlight the importance of the local microenvironment in both phenotypic and functional specialization of macrophages in atherosclerosis and elaborate on the need for spatial multiomics approaches to provide a better understanding of the different macrophage subsets' roles in the pathogenesis of atherosclerosis.
Disciplines :
Cardiovascular & respiratory systems
Author, co-author :
Wieland, Elias B ; Cardiovascular Research Institute Maastricht, Experimental Vascular Pathology, Department of Pathology, Maastricht University Medical Centre+, Maastricht, the Netherlands
Kempen, Laura ; Université de Liège - ULiège > Département des sciences fonctionnelles (DSF) ; Cardiovascular Research Institute Maastricht, Experimental Vascular Pathology, Department of Pathology, Maastricht University Medical Centre+, Maastricht, the Netherlands
Donners, Marjo Mpc; Cardiovascular Research Institute Maastricht, Experimental Vascular Pathology, Department of Pathology, Maastricht University Medical Centre+, Maastricht, the Netherlands
Biessen, Erik Al; Cardiovascular Research Institute Maastricht, Experimental Vascular Pathology, Department of Pathology, Maastricht University Medical Centre+, Maastricht, the Netherlands ; Institute for Molecular Cardiovascular Research, RWTH Aachen University, Aachen, Germany
Goossens, Pieter; Cardiovascular Research Institute Maastricht, Experimental Vascular Pathology, Department of Pathology, Maastricht University Medical Centre+, Maastricht, the Netherlands
Language :
English
Title :
Macrophage heterogeneity in atherosclerosis: A matter of context.
This work has been supported by the Dutch Heart Foundation (Dekker 2020T042 to P.G.). The authors would like to thank Catherine Labarca (Lipid Studios) for creating the scientific illustrations for this review.
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