1 Altered immune cell metabolism in atherosclerosis
In an inflammatory milieu, immune cells are extremely active and must
meet various metabolic demands(Ketelhuth and Hansson, 2016; Tabas and
Bornfeldt, 2016). Immune cells are capable of adapting to differences in
environmental cues (e.g., oxygen, nutrition, growth hormones) as well as
energy and biosynthetic requirements upon activation (metabolic
reprogramming)(O’Neill et al., 2016). Immune cells have at least seven
primary cellular metabolic processes documented(Cole et al., 2018;
Winkels et al., 2018),namely immune cell survival, growth, and
activation are regulated by the interconnected pathways of glycolysis,
the pentose phosphate pathway (PPP), the tricarboxylic acid (TCA) cycle,
oxidative phosphorylation (OXPHOS), mitochondrial fatty acid -oxidation
(FAO), fatty acid synthesis, and amino acid metabolism. Metabolic
alterations in immune cells, also known as metabolic flexibility or
reprogramming, not only occur in response to inflammatory mediators and
other environmental cues, but are also essential for immune cells to
induce inflammation, terminate the inflammatory response, and initiate
tissue healing(Ridker et al., 2017).Metabolic changes are the key
characteristics that determine the function of immune cells and
subsequent disease progression. New insights into the molecular
processes that drive immunity and inflammation reveal that changes in
intracellular metabolic pathways are significant drivers of immune cell
survival, proliferation, and function. Recent research indicates that
immunometabolism plays a crucial role in the course of diseases such as
atherosclerosis(Hotamisligil, 2017). LDL particles may be converted to
oxidized (ox) LDL in the vascular intima, which stimulates blood
arteries and innate immune cells. Therefore, antigens generated from
LDL-derived peptides stimulate T cell activation in atherosclerosis and
exacerbate the inflammatory response,and then enhance plaque formation,
ultimately resulting in unstable plaque rupture, which may cause
thrombosis and acute clinical symptoms such as myocardial infarction and
stroke.