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DOI: 10.1160/TH16-08-0593
Pathophysiological relevance of macrophage subsets in atherogenesis
Financial support: This study was supported by European Commission (FP7-INNOVATION I HEALTH-F2–2013–602114; Athero-B-Cell: Targeting and exploiting B cell function for treatment in cardiovascular disease). This work was supported by a Swiss National Science Foundation Grant to Dr. F. Montecucco (#310030_152639/1).Publikationsverlauf
Received:
01. August 2016
Accepted after minor revision:
12. September 2016
Publikationsdatum:
01. Dezember 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/201701/lookinside/thumbnails/10-1160-th16-08-0593-1.jpg)
Summary
Macrophages are highly heterogeneous and plastic cells. They were shown to play a critical role in all stages of atherogenesis, from the initiation to the necrotic core formation and plaque rupture. Lesional macrophages primarily derive from blood monocyte, but local macrophage proliferation as well as differentiation from smooth muscle cells have also been described. Within atherosclerotic plaques, macrophages rapidly respond to changes in the microenvironment, shifting between pro- (M1) or anti-inflammatory (M2) functional phenotypes. Furthermore, different stimuli have been associated with differentiation of newly discovered M2 subtypes: IL-4/IL-13 (M2a), immunecomplex (M2b), IL-10/glucocorticoids (M2c), and adenosine receptor agonist (M2d). More recently, additional intraplaque macrophage phenotypes were also recognized in response to CXCL4 (M4), oxidized phospholipids (Mox), haemoglobin/haptoglobin complexes (HAmac/M(Hb)), and heme (Mhem). Such macrophage polarization was described as a progression among multiple phenotypes, which reflect the activity of different transcriptional factors and the cross-talk between intracellular signalling. Finally, the distribution of macrophage subsets within different plaque areas was markedly associated with cardiovascular (CV) vulnerability. The aim of this review is to update the current knowledge on the role of macrophage subsets in atherogenesis. In addition, the molecular mechanisms underlying macrophage phenotypic shift will be summarised and discussed. Finally, the role of intraplaque macrophages as predictors of CV events and the therapeutic potential of these cells will be discussed.
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