Macrophage heterogeneity in atherosclerosis: A matter of context

Author:

Wieland Elias B1ORCID,Kempen Laura JAP123,Donners Marjo MPC1,Biessen Erik AL14,Goossens Pieter1

Affiliation:

1. Cardiovascular Research Institute Maastricht, Experimental Vascular Pathology, Department of Pathology Maastricht University Medical Centre+ Maastricht the Netherlands

2. Laboratory of Immunology and Vaccinology Faculty of Veterinary Medicine FARAH, ULiège Liège Belgium

3. Laboratory of Immunophysiology GIGA Institute Liege University Liège Belgium

4. Institute for Molecular Cardiovascular Research RWTH Aachen University Aachen Germany

Abstract

AbstractDuring 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.

Funder

Hartstichting

Publisher

Wiley

Subject

Immunology,Immunology and Allergy

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