Local proliferation dominates lesional macrophage accumulation in atherosclerosis

By Clinton S. Robbins, I. Hilgendorf, G. Weber, I. Theurl, Y. Iwamoto, Jose-Luiz Figueiredo, Rostic Gorbatov, G. Sukhova, Louisa M. S. Gerhardt, D. Smyth and 10 more. Nature Medicine, 2013

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During the inflammatory response that drives atherogenesis, macrophages accumulate progressively in the expanding arterial wall. The observation that circulating monocytes give rise to lesional macrophages has reinforced the concept that monocyte infiltration dictates macrophage buildup. Recent work has indicated, however, that macrophage accumulation does not depend on monocyte recruitment in some inflammatory contexts. We therefore revisited the mechanism underlying macrophage accumulation in atherosclerosis. In murine atherosclerotic lesions, we found that macrophages turn over rapidly, after 4 weeks. Replenishment of macrophages in these experimental atheromata depends predominantly on local macrophage proliferation rather than monocyte influx. The microenvironment orchestrates macrophage proliferation through the involvement of scavenger receptor A (SR-A). Our study reveals macrophage proliferation as a key event in atherosclerosis and identifies macrophage self-renewal as a therapeutic target for cardiovascular disease.

Subfields: Epidemiology, Immunology

View Paper: https://www.semanticscholar.org/paper/12fa27154d3186c98da8583a0e6fe2dab5bf0606

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Citations in the corpus

Atherosclerosis: Recent developments (2022, background): “Mouse studies suggest that the abundance of macrophages in early lesions is determined by recruitment but that in more advanced lesions it results largely from macrophage proliferation (Robbins et al., 2013).”
Macrophage Phenotype and Function in Different Stages of Atherosclerosis (2016, neutral): “Local proliferation of macrophages can also contribute to the accumulation of cells, at least in fatfed mice and rabbits,(31,108,109) although monocyte recruitment is likely to dominate in early lesions, whereas macrophage proliferation takes on a more important role in more advanced lesions.(31) Ar”
Macrophages: development and tissue specialization. (2015, background): “However, it was recently shown that maintenance and expansion of the pool of lesional monocyte-derived macrophages in experimental atheromata can involve the local proliferation of these cells rather than continuous de novo monocyte influx (83).”
From Monocytes to M1/M2 Macrophages: Phenotypical vs. Functional Differentiation (2014, background): “However, it was recently demonstrated that the maintenance and accumulation of monocyte-derived macrophages in atherosclerotic plaques mainly depend on local proliferation of bone marrow-derived macrophages rather than on the influx of circulating monocytes (127, 159).”
Macrophage heterogeneity in liver injury and fibrosis. (2014, background): “In conditions of atherosclerosis or peritonitis, infiltrated monocyte-derived as well as tissue resident macrophages locally proliferated in response to inflammatory stimuli [36,37].”
Monocyte-Macrophages and T Cells in Atherosclerosis (2017, neutral): “Macrophage proliferation occurs in atherosclerosis, particularly in advanced plaques (Sakai et al., 2000; Robbins et al., 2013), but the mechanisms and consequences of lesional macrophage proliferation remain largely unknown.”
Inflammation and atherosclerosis: signaling pathways and therapeutic intervention (2022, background): “Macrophages in plaques are not exclusively derived from monocytes, but mainly rely on their own local proliferation.(62) Macrophages exert atheroprotective effects under homeostatic conditions, through both the clearance of lipoprotein by endocytosis and apoptotic cells by phagocytosis or efferocyto”