Atherosclerosis
In addition to microbial products, endogenous non-microbial stimulus ox-LDL and lipoprotein (a) also induce monocyte/macrophage immune memory and play important roles at different stages of atherosclerosis28, 58. In this context, trained human monocytes have been found to switch to an enduring pro-atherogenic macrophage phenotype via epigenetic histone modifications associated with the downregulation of H3K4me3 on the promoters of pro-inflammatory cytokines and a metabolic shift toward increased glycolysis. When stimulated secondarily by TLR2 and TLR4 ligands, there is a substantial increase in the production of pro-atherogenic factors, such as TNF-α, IL-1β, IL-6, and monocyte chemoattractant protein-1 (MCP-1), which may lead to arteriosclerotic plaque instability and exacerbate atherosclerosis28, 59-61.