NLRP3 inflammasome as a novel therapeutic target for heart failure

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.

Figure 2. Heart failure caused by NLRP3 inflammasome corpuscle activation. Inflammatory factors produced by NLRP3 trigger cardiac inflammation by recruiting macrophages and subsequent T cells, leading to fibrosis, adverse cardiac remodeling, and heart failure. It can also induce cardiomyocytes scorch death and finally promote myocarditis and remodeling.