Figure 1.

Monocyte and macrophage heterogeneity in steady state and cardiovascular disease. During homeostasis, Ly6C^hi monocytes circulate through blood vessels and infiltrate tissue, where they give rise to CCR2⁺ MΦs, while Ly6C^lo monocytes patrol the vasculature. Cardiac MΦs are further composed of monocyte-independent self-renewing TIMD4⁺LYVE1⁺ and MHC-II⁺ resident MΦs, which localize preferentially near blood vessels and nerve bundles, respectively. During myocardial infarction, there is increased monopoiesis and release of Ly6C^hi monocytes from the spleen and bone marrow, which are recruited to the injured heart and give rise to diverse MΦ subsets. Whether these MΦ subsets are a spectrum of activation states or arise via pre-defined monocyte fates, such as Ym1⁺ or CXCR6^hi/Slan^hi Ly6C^lo monocytes as identified in other disease models, is not known. Conversely, there is a loss of TIMD4⁺LYVE1⁺ and MHC-II⁺ resident MΦs. In the vessels, the intima is lined with CD11c⁺ MΦs and the adventitia contain TIMD4⁺LYVE1⁺ MΦs and other undefined resident MΦ populations. In atherosclerosis, TREM2^hi MΦs and inflammatory monocyte-derived MΦs accumulate in the intima, expand via self-renewal and participate in plaque growth. How this fate is defined and the contribution of CXCR6^hi/Slan^hi Ly6C^lo monocytes, found in the circulation of patients correlating with disease severity, is unknown. Mϕ, macrophage.