Fig. 3.

Metabolic status of immune cells differs from physiological to atherosclerotic conditions. Under physiological conditions, circulating monocytes and lymphocytes (both T and B cells) mainly rely on oxidative metabolism (OXPHOS). During atherosclerosis, increased cholesterol levels trigger lipid accumulation both in circulating monocytes as well as in atherosclerotic plaque macrophages thus leading to cell reprogramming and the switch from oxidative metabolism to anaerobic glycolysis, which in turn guides their pro-inflammatory activation. In dendritic cells, cholesterol accumulates in plasma membrane and cytoplasm leading to increased antigen presenting function and pro-inflammatory cytokines release. In adaptive immune cells, lipid overload and the presence of atherosclerosis-related antigens contribute to B and T cells activation, favouring OSE antibodies production in B cells and the polarization toward an effector phenotype in T cells; both cells are characterized by faster glycolytic metabolism and increased demand of cholesterol to sustain cell proliferation.