Macrophage heterogeneity in atherosclerosis: A matter of context

Area of Science:

• Immunology
• Cardiovascular Biology
• Cell Biology

Background:

• Macrophages play a central role in atherogenesis, processing lipids and driving inflammation.
• The traditional view of macrophages as simply inflammatory or anti-inflammatory is insufficient to explain their complex roles in atherosclerosis.
• Recent advances reveal significant macrophage heterogeneity and functional specialization in pathological conditions like atherosclerosis.

Purpose of the Study:

• To review the origins and functional specialization of macrophages in atherosclerotic plaques.
• To discuss the phenotypic diversity and spatial distribution of macrophages in both mouse and human atherosclerosis.
• To highlight the influence of the local microenvironment on macrophage specialization and emphasize the need for spatial multiomics.

Main Methods:

• Review of current literature on macrophage biology in atherosclerosis.
• Analysis of findings from single-cell RNA sequencing studies in murine and human atherosclerosis.
• Synthesis of data on the impact of the microenvironment on macrophage phenotype and function.

Main Results:

• Macrophages exhibit remarkable heterogeneity and functional specialization within atherosclerotic plaques.
• Diverse sources contribute to macrophage accumulation during atherogenesis.
• Distinct macrophage subsets with specific functions and spatial localizations exist in atherosclerosis.

Conclusions:

• The complex roles of macrophages in atherosclerosis necessitate moving beyond simplistic inflammatory paradigms.
• Understanding macrophage origins, heterogeneity, and microenvironmental interactions is crucial for deciphering pathogenesis.
• Future research should employ spatial multiomics to elucidate the precise functions of different macrophage subsets in atherosclerosis.