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.