OXIDATIVE STRESS-INDUCED IMMUNOMETABOLISM IN ATHEROSCLEROSIS
Atherosclerosis is a chronic lipid-driven inflammatory disease of
arterial vessels in which cholesterol-rich lipoproteins, notably LDL,
accumulate subendothelial regions of the arterial wall(Wu et al., 2020)
that it may be converted to oxidized (ox) LDL in the vascular intima,
stimulating blood arteries and innate immune cells(Paiva and Bozza,
2014). Moreover, antigens generated from LDL-derived peptides stimulate
T cell activation in atherosclerosis and exacerbate the inflammatory
response. Persistent innate and adaptive immune responses enhance plaque
formation, ultimately resulting in unstable plaque rupture, which may
cause thrombosis and acute clinical symptoms such as myocardial
infarction and stroke(Liu et al., 2017). Clinically, atherosclerotic
plaques are distinguished by the presence of macrophages and regulatory
T cells (Tregs) in excess. Relevant research shows that oxidative
stress-activated macrophages and T cells have a greater metabolic
propensity for aerobic glycolysis than mitochondrial metabolism(Raud et
al., 2018). In contrast, the unoxidized activated immunoregulatory
cells, such as M2 macrophages and Tregs, inhibit the metabolism of fatty
acids, including oxidation and oxidative phosphorylation. Figure 1
depicts the metabolic alterations generated by oxidative stress in
atherosclerosis in macrophages and Treg cells.