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.