Figure 2.

Monocyte differentiation and macrophage polarization. Monocytes are derived from the hematopoietic precursors of bone marrow or spleen and produce the classic lymphocyte antigen 6C (LY6C) ^high in mice (corresponding to human CD14^high CD16^low monocytes), and nonclassical-LY6C^low in mice (corresponding to human CD14^low CD16^high monocytes). LY6C^high monocytes highly express CCR2, which can be recruited by chemokines (such as CCL2) to inflammatory sites (including atherosclerotic plaques) to play a pro-inflammatory effect (it is considered to be the precursor of M1 macrophages). Hypercholesterolemia promotes the production of LY6C^high monocytes by inducing the proliferation of bone marrow precursors. LY6C^low monocytes (considered to be the precursor of M2 macrophages) highly express CX₃CR1. These monocyte subpopulations use different chemokine-chemokine receptor pairs to penetrate into the inner membrane, and then differentiate into macrophages in the inner membrane (LY6C^high is more likely to differentiate into M1 macrophages, while LY6C^low is more likely to differentiate M2 macrophages). M1 macrophages amplify the inflammatory effect by secreting pro-inflammatory cytokines. M2 macrophages help tissue repair by secreting anti-inflammatory cytokines and collagen. AP-1, activator protein 1; Arg1, arginase 1; CCL, C−C motif chemokine; CCR, C-C chemokine receptor; CD, cluster of differentiation; FIZZ1, found in inflammatory zone 1; HIF1α, hypoxia-inducible factor 1α; ICAM1, intercellular adhesion molecule-1; INFγ, interferon-γ; iNOS, inducible nitric oxide synthase; IL, Interleukin; IL-1R, Interleukin 1 receptor; KLF4, Krüppel-like factor 4; LPS, lipopolysaccharide; NO, nitric oxide; NF-κB, nuclear factor kappa B; PPAR, peroxisome proliferator activated receptor; STAT, Signal transducer and activator of transcription; VCAM1, vascular cell adhesion protein 1.