Figure 1.

Activation mechanism of NLRP3 in heart failure: PAMPs and DAMPS trigger the formation of polyinflammatory complex composed of NLRP3, ASC, and pro-caspase-1. The disturbance of intestinal metabolites SCFAs, LPS, TMAO, and bile acid can activate NLRP3 inflammasome through TLR4. Energy metabolism was disrupted, ATP production was decreased, and NLRP3 inflammasome was activated by P2X7. At the same time, glucose metabolism disorder, activation of AMPK, resulting in ROS production, through TXNIP activate NLRP3 inflammasome. The release of IL-1β and IL-18 after the activation of NLRP3 inflammasome causes heart failure, whereas intestinal metabolism disorders and energy metabolism disorders also cause heart failure; therefore, so NLRP3 inflammasome is the central link of heart failure.