Table 2. Characteristics of macrophages with a M1, M2, and M(Hb) phenotype.

Multiple macrophage phenotypes have been detected in atherosclerotic lesions, including macrophages with a M1, M2, and M(Hb) phenotype. The different types of macrophages have different effects on plaque progression. IFNγ, Interferon gamma; IL, Interleukin; TNFα, Tumor necrosis factor alpha; iNOS, inducible nitric oxide synthase; PDGF, Platelet-derived growth factor; MMP, Matrix metallopeptidase; VEGF-A, vascular endothelial growth factor; HIF, Hypoxia inducible factor; ABC transporter; ATP-binding cassette transporter; oxLDL, Oxidized low-density lipoprotein; FPN, Ferroportin; HO-1, Heme oxygenase 1.

	Classically activated M1 macrophages	Alternatively activated M2 Macrophages	Hemorrhage-associated M(Hb) macrophages
Activation by	INFγ, fatty acids, oxidized lipids79	IL-4, IL-10, IL-1387	Hemoglobin97
Characteristics	Pro-inflammatory80,85,86 Promote inflammation Promote collagen hydrolysis ↑TNFα, IL-1, IL-6, IL-12, iNOS ↑TGF-β, PDGF production ↑secretion of MMP1, MMP3 and MMP9	Anti-inflammatory88,89,93,94 Promote tissue repair and vascular stalility Promote collagen production ↑IL-10, arginase-1, CD206 ↑ornithine, VEGF-A production	Anti- as well as pro-inflammatory properties97,105,106 Promote tissue repair and vascular stability Promote angiogenesis, vessel permeability, & inflammatory cell recruitment ↑IL-10, CD206 ↑HIF-α and VEGF-A
Lipid handling	Increased intracellular lipid levels84 ↑oxLDL scavenger receptors CD36 ↑foam ceil formation	Decreased intracellular lipid levels93,96 ↑ABC transporters ↓CD36 ↑efferocytosis	Decreased intracellular lipid levels97 ↑ABC transporters ↓CD36
Iron phenotype	Iron sequestration phenotype82,83 ↑Ferritin ↓FPN, HO-1, CD163 ↑ intracellular iron	Iron releasing phenotype83,90 ↑Ferritin ↓FPN, HO-1, CD163 ↑intracellular iron	Iron releasing phenotype103,104 ↓Ferritin ↑FPN, HO-1, CD163 ↓intracellular iron
Atherosclerosis	Pro-atherogenic	Atheroprotective	Pro-atherogenic and Atheroprotective