Macrophage heterogeneity in atherosclerosis: A matter of context

Abstract: 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.

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch

Bibliographic citation
Macrophage heterogeneity in atherosclerosis: A matter of context ; day:09 ; month:11 ; year:2023 ; extent:9
European journal of immunology ; (09.11.2023) (gesamt 9)

Creator
Wieland, Elias B.
Kempen, Laura JAP
Donners, Marjo MPC
Biessen, Erik AL
Goossens, Pieter

DOI
10.1002/eji.202350464
URN
urn:nbn:de:101:1-2023111014083773877542
Rights
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Last update
14.08.2025, 11:02 AM CEST

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Associated

  • Wieland, Elias B.
  • Kempen, Laura JAP
  • Donners, Marjo MPC
  • Biessen, Erik AL
  • Goossens, Pieter

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