Figure 6. NLRP3 inflammasome activation in diabetic atherosclerosis.
Intracellular hyperglycemia-induced ROS in monocytes and vascular endothelial cells increases RAGE expression, which heterodimerizes with TLR4. Signaling from this complex causes NFκB-mediated transcription of inactive NOD-like receptor family, pyrin domain-containing 3 (NRLP3), pro-IL-1β, and pro-IL-18. Increased intracellular Ca++ triggers oligomerization of inactive NLRP3, associated with apoptosis-associated speck-like protein (ASC), and pro-caspase-1. This activated inflammsome complex catalyzes the conversion of procaspase-1 to caspase-1, and of pro-IL-1β and pro-IL-18 to mature IL-1β and IL-18. S100A8/12, calgranulin A/B heterodimer ligand for RAGE.