Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Editorial
. 2024 Jan 19;134(2):186-188.
doi: 10.1161/CIRCRESAHA.123.324011. Epub 2024 Jan 18.

Macrophage Heterogeneity and Efferocytosis: Beyond the M1/M2 Dichotomy

Prabhash Kumar Jha  1 , Masanori Aikawa  1   2   3 , Elena Aikawa  1   2
Affiliations
Editorial

Macrophage Heterogeneity and Efferocytosis: Beyond the M1/M2 Dichotomy

Prabhash Kumar Jha et al. Circ Res. .
No abstract available

Keywords: Editorials; cell death; efferocytosis; inflammation; macrophages; osteoclasts.

PubMed Disclaimer

Conflict of interest statement

Disclosures None.

Figures

None
Macrophage heterogeneity and necrotic core formation.
The formation of a necrotic core within an atherosclerotic plaque is influenced by a delicate balance between inflammation and efferocytosis. Heterogeneous macrophage subpopulations, each characterized by distinct functional phenotypes, are revealed within atherosclerotic plaques through single-cell sequencing. The existence of one or more subset populations within a specifically activated macrophage subset, coupled with an imbalanced representation of another subset, can significantly shape the trajectory of disease progression. Under pro-atherogenic conditions (left panel), a larger necrotic core forms due to two primary factors. Firstly, there is an expansion of the subset of inflammatory macrophages, releasing an excess of inflammatory factors, orchestrating the recruitment of immune cells, and perpetuating an inflammatory milieu. Secondly, there is a reduction in the subset of efferocytic macrophages, leading to inadequate clearance of apoptotic cells. Lv and colleagues demonstrated that CD147 promotes pro-atherogenic conditions via regulation of inflammation and efferocytosis (left panel). Conversely, in an anti-atherogenic environment (right panel), the opposite unfolds. Understanding and controlling of the delicate equilibrium between inflammation and efferocytosis represent focal points of research aimed at devising therapeutic strategies to stabilize atherosclerotic plaques and mitigate the risk of complications linked to plaque rupture. Strategies that bolster efferocytosis or temper excessive inflammation emerge as promising avenues for intervening in atherosclerosis. Mφ indicates Macrophage; TAM, Tyro3, Axl, and MerTK; Gas6, growth arrest specific-6.
See this image and copyright information in PMC

Comment on

References

    1. Rogers MA, Aikawa M and Aikawa E. Macrophage Heterogeneity Complicates Reversal of Calcification in Cardiovascular Tissues. Circ Res. 2017;121:5–7. - PMC - PubMed
    1. Barrett TJ. Macrophages in Atherosclerosis Regression. Arterioscler Thromb Vasc Biol. 2020;40:20–33. - PMC - PubMed
    1. Fredman G and MacNamara KC. Atherosclerosis is a major human killer and non-resolving inflammation is a prime suspect. Cardiovasc Res. 2021;117:2563–2574. - PMC - PubMed
    1. Gerlach BD, Ampomah PB, Yurdagul A Jr., Liu C, Lauring MC, Wang X, Kasikara C, Kong N, Shi J, Tao W, et al. Efferocytosis induces macrophage proliferation to help resolve tissue injury. Cell Metab. 2021;33:2445–2463 e8. - PMC - PubMed
    1. Kojima Y, Volkmer J-P, McKenna K, Civelek M, Lusis AJ, Miller CL, Direnzo D, Nanda V, Ye J, Connolly AJ, et al. CD47-blocking antibodies restore phagocytosis and prevent atherosclerosis. Nature. 2016;536:86–90. - PMC - PubMed