Lipid-induced death of macrophages: Implication for destabilization of atherosclerotic plaques

In recent decades, the incidence of atherosclerosis in Western society has been on the rise. Lipid particles, of which low density lipoprotein (LDL) is the most studied, accumulate in the intima of blood vessels and lead to inflammatory processes. Leukocytes, mostly macrophages, are recruited from circulating blood to the vessel walls. After they are overexposed to lipids and transform to foam cells, cell death processes take place. In macrophages, the exposure to lipids is known to trigger cell deaths of both apoptotic and necrotic types. External, receptor-dependent, and internal mitochondria-affecting apoptotic death pathways are involved in these processes. Although oxidized LDL is known as a major factor for plaque formation, triacylglycerols (TGs) are increasingly believed to be independently associated with coronary heart disease. Accumulation of intracellular TGs causes elevation of reactive oxygen species (ROS), probably of mitochondrial sources, and cell death. In this chapter, the role of macrophage cell death in atherogenic plaque instability and the specific effects of TG in macrophage lipotoxicity are discussed.