Figure 1.

Mechanisms of NLRP3 inflammasome activation in heart failure. Myocardial infarction (MI), ischemia or ischemia/reperfusion (I/R) injury induces cardiomyocytes to release ROS, ATP and mtDNA. ROS mediates autocrine and paracrine activation and nuclear translocation of NF-κB, which regulates the transcription of pro-IL-1β and pro-IL-18. mtDNA directly primes NLRP3 and ATP via binding to P2X₇ receptors and leads to potassium efflux, a trigger for the assembly of NLRP3 inflammasome. These collective effects result in activation of the NLRP3 inflammasome-associated caspase-1, which processes pro-IL-1β and pro-IL-18 into mature IL-1β and IL-18 and can exacerbate local inflammation. It can also be released into circulation to mediate endocrine effects. ATP, adenosine triphosphate; IL, interleukin; mtDNA, mitochondrial DNA; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; NLRP3, NLR family, pyrin domain containing 3; ROS, reactive oxygen species; K⁺, potassium.