Abstract
It is well recognized that macrophages in many contexts in vitro and in vivo display a spectrum of inflammatory features and functional properties. A convenient system to group together different subsets of macrophages has been the M1 (inflammatory)/M2 (anti-inflammatory) classification. In addition to other sites of inflammation, it is now established that atherosclerotic plaques contain both M1 and M2 macrophages. We review results made possible by a number of recent mouse models of atherosclerotic regression that, taken with other literature, have shown the M1/M2 balance in plaques to be dynamic, with M1 predominating in disease progression and M2 in regression. The regulation of the macrophage phenotype in plaques and the functional consequences of the M1 and M2 states in atherosclerosis will also be discussed.
Highlights
Atherosclerotic cardiovascular diseases, which include myocardial infraction and stroke, are the most common causes of morbidity and mortality in western society and will soon be the same world-wide
In addition to the M1 and M2 macrophages, oxidized phospholipids present in oxidized LDL induce a macrophage phenotype that is distinct from M1 or M2 phenotypes and that has been termed Mox; these macrophages are characterized by the increases in the expression of nuclear factor erythroid 2-related factor 2 (NRF2)-dependent genes and in reactive oxygen species, and are found in the progressing plaques [18]
We have recently reported that murine bone marrow derived-macrophages (BMDM) not loaded with cholesterol will increase their M2 marker expression when incubated with HDL [81] [though in human monocytes this was not found to be the case [82]], and Latz and colleagues have found that HDL will induce in macrophages the transcriptional regulator ATF3, a repressor of a number of inflammatory factors [83]
Summary
Atherosclerotic cardiovascular diseases, which include myocardial infraction and stroke, are the most common causes of morbidity and mortality in western society and will soon be the same world-wide. Atherosclerosis represents a failure to resolve the inflammatory response in the arterial wall initiated by the retention of apolipoprotein B (apoB)-containing lipoproteins [1] These lipoproteins are taken up by tissue macrophages, which become engorged with cholesterol (foam cells) and activated. Admitting the complexity of macrophage biology, for the purposes of this review, we have restricted ourselves to considering how aspects of macrophage polarization in the M1/M2 classification system [8] relate to atherosclerosis progression and regression In this system, which is influenced by the Th1 and Th2 classification of lymphocytes, macrophages can be grossly divided into pro-inflammatory, M1 cells and anti-inflammatory, M2 cells based mainly on in vitro criteria [9]. Based on the role of M2 macrophages in wound www.frontiersin.org
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