Figure 8. Schematic depiction of the links between macrophage p62, polyubiquitinated protein inclusion body formation, and atherosclerosis.

p62 is essential for the clearance of polyubiquitinated proteins by autophagy. Although atherogenic lipids impair this degradative process by affecting lysosomal degradation, the subsequent formation of p62-positive inclusion bodies are less cytotoxic, which is at least partly due to more efficient p62-dependent clearance of inflammasomes (left). In the absence of p62, inclusion bodies cannot form leading to the accumulation of poorly formed polyubiquitinated protein aggregates and increased numbers of inflammasomes. These defects in turn initiate deleterious cellular pathways such as IL-1β secretion and apoptosis which exacerbate atherosclerotic progression (right).