Abstract
The emerging understanding of macrophage subsets and their functions in the atherosclerotic plaque has led to the consensus that M1 macrophages are pro-atherogenic while M2 macrophages may promote plaque stability, primarily though their tissue repair and anti-inflammatory properties. As such, modulating macrophage function to promote plaque stability is an exciting therapeutic prospect. This review will outline the involvement of the different macrophage subsets throughout atherosclerosis progression and in models of regression. It is evident that much of our understanding of macrophage function comes from in vitro or small animal models and, while such knowledge is valuable, we have much to learn about the roles of the macrophage subsets in the clinical setting in order to identify the key pathways to target to possibly promote plaque stability.Electronic supplementary materialThe online version of this article (doi:10.1186/s40169-014-0042-1) contains supplementary material, which is available to authorized users.
Highlights
The main cause of cardiovascular disease is the formation of atherosclerotic plaques within the blood vessel wall
Type 2 macrophage (M2) markers such as Arg I, Mannose receptor (MR), CD163, C-lectin and FIZZ1 [111]. This increase in M2 macrophages is evident in other models of plaque regression including transplant of the atherosclerosed vessel into normal cholesterolaemic mice [112] and induction of regression by high density lipoprotein (HDL) [113]. Whether these changes involved a phenotypic conversion of Type 1 macrophage (M1) to M2 macrophages is not clear, but it has been suggested to occur in the ApoE-/- mouse as seen by the presence of macrophages double staining with Arg I (M2) and Arg II (M1) [68], though it should be noted that the specificity of Arg I for M2 macrophages is in question [20]
A spectrum of macrophage phenotypes is present in the atherosclerotic plaque with each, in some way, impacting plaque stability
Summary
The main cause of cardiovascular disease is the formation of atherosclerotic plaques within the blood vessel wall. Though M2 macrophages may theoretically have a greater ability to take up lipid in the plaque, the increasingly pro-inflammatory environment may skew monocyte to macrophage differentiation towards that of an M1 phenotype This skewing would account for the reported absence of M2 foam cells in advanced human lesions [40], or their location distant from the core [75]. This increase in M2 macrophages is evident in other models of plaque regression including transplant of the atherosclerosed vessel into normal cholesterolaemic mice [112] and induction of regression by HDL [113] Whether these changes involved a phenotypic conversion of M1 to M2 macrophages is not clear, but it has been suggested to occur in the ApoE-/- mouse as seen by the presence of macrophages double staining with Arg I (M2) and Arg II (M1) [68], though it should be noted that the specificity of Arg I for M2 macrophages is in question [20]. A greater understanding of macrophage function in the plaque, their plasticity (or lack thereof) and the pathways involved is required to ensure that a plaque stabilising form can be promoted
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