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.