Macrophage Phenotypes and Their Modulation in Atherosclerosis

Abstract

Atherosclerosis is the result of a chronic inflammatory response in the arterial wall related to uptake of low-density lipoprotein by macrophages and their subsequent transformation in foam cells. Monocyte-derived macrophages are the principal mediators of tissue homeostasis and repair, response to pathogens and inflammation. However, macrophages are a homogeneous cell population presenting a continuum phenotypic spectrum with, at the extremes, the classically Th-1 polarized M1 and alternatively Th-2 polarized M2 macrophage phenotypes, which have been well described. Moreover, M2 macrophages also present several subtypes often termed M2a, b, c and d, each of them expressing specific markers and exhibiting specialized properties. Macrophage plasticity is mirrored also in the atherosclerotic lesions, where different stimuli can influence the phenotype giving rise to a complex system of subpopulations, such as Mox, Mhem, M(Hb) and M4 macrophages. An abundant literature has described the potential modulators of the reciprocal skewing between pro-inflammatory M1 and anti-inflammatory M2 macrophages including lesion stage and localization, miRNA, transcription factors such as PPARγ, KLF4 and NR4A family members, high-density lipoproteins and plaque lipid content, pathways such as the rapamycin-mTOR1 pathway, molecules such as thioredoxin-1, infection by helminths and irradiation. We hope to provide an overview of the macrophage phenotype complexity in cardiovascular diseases, particularly atherosclerosis.

Pericoronary Adipose Tissue as Possible Supply Site and Storage for Lipoproteins in Human Coronary Artery

“…Among them, M1-macrophages are considered as atherogenic whereas M2-macrophages as anti-atherogenic, based mostly on the findings in animals or cultured cells. [17] To our knowledge, there are no reports on storage of oxLDL, HDL or ApoA1 in human PCAT. In our unpublished study, a certain group of CD11c (+) -macrophages (M1-macrophages) contained oxLDL or ApoA1 but not HDL (Figure 4).…”

Macrophages: Tissue-Resident Determinants of Immunomodulation

“…Several "variations" on the theme of M2 MΦs have been described on the basis of activation and phenotype: these include M2a (alternative), M2b (type II), M2c (deactivated), M2d and regulatory MΦs [6][7][8][9][10]. In addition, some MΦ subsets have been also described in pathological environments which include M4, Mox, HA-mac, M(Hb) and Mhem [11], all of which represent a spectrum of effector functionality, where M4 is closer to the M1 phenotype on the basis of low IL-10 expression and Mox, HA-mac, Mhem, M(Hb) are closer to the M2 phenotype (IL-10 hi , scavenger receptor hi ).…”

“…Atherosclerosis research has resulted in the description of M4, Mox, HA-mac, M (Hb) and Mhem [11], all of which are conditioned by the pro-inflammatory environment associated with atherosclerotic lesions. Mucosal macrophages are also defined by their environment: intestinal MΦs generally exhibit an anti-inflammatory suppressive, tolerisable functional phenotype defined by IL-10, TGFβ and phagocytic receptors (CD36, CD68, CD206) which resembles that of an M2-like subset [13].…”

Evaluation of Serum Lipid Profile Level and Gamma-Glutamyltransferase Activity as a Biomarker for Coronary Artery Disease in Sudanese Patients

“…Coronary arteriosclerosis comprises a series of inflammatory responses at cellular and molecular level (Gomes et al, 2010). It is a chronic inflammatory disease affecting blood vessels, in which the arterial wall thickens because of the formation of an atheromatous plaque (De Paoli et al, 2014).…”

“…Macrophages clear the excess modified lipoproteins that accumulate in the neointima and as a consequence, the macrophages become engorged with lipids and can no longer emigrate from the plaque (De Paoli et al, 2014). Risk factors for coronary artery disease have included high blood pressure, cigarette smoking, increased low-density lipoprotein concentration, decreased high-density lipoprotein concentration, and diabetes (Homoud, 2008).…”