Monocyte heterogeneity in human cardiovascular disease

Atherosclerosis has been characterized as an inflammatory process, in which monocytes and monocyte-derived macrophages are of paramount importance. Contrasting with their established role in atherosclerosis, monocytes have not unanimously been found to predict cardiovascular events in large epidemiological studies. However, in these studies human monocyte heterogeneity has been largely overlooked so far. Three human monocyte subsets can be distinguished: classical CD14++CD16−, intermediate CD14++CD16+ and nonclassical CD14+CD16++ monocytes. Of note, correct enumeration of subset counts requires appropriate staining and gating strategies that encompass a pan-monocytic marker (e.g. HLA-DR or CD86). In experimental studies on murine atherogenesis a monocyte subset-specific contribution to atherosclerosis has been established. However, major interspecies differences in atherogenesis itself, as well as in the immune system (including monocyte subset phenotype and distribution) preclude a direct extrapolation to human pathology. Experimental and pilot clinical studies point to a prominent involvement of intermediate CD14++CD16+ monocytes in human atherosclerosis. Future clinical studies should analyze monocyte heterogeneity in cardiovascular disease. If a specific contribution of intermediate monocytes should be confirmed, immunomodulation of this monocyte subset could represent a future therapeutic target in atherosclerosis.