Figure 1.

The comprehensive process by which NLRP3 inflammasome activation occurs, resulting in myocardial cell hypertrophy and inflammation in patients with heart failure. During the priming step, various stimuli such as PAMPs, DAMPs, IL-1, and TNF trigger the phosphorylation and degradation of inhibitor of NF-kB, initiating the activation of the NF-kB pathway. This pathway subsequently promotes the transcription of NLRP3, pro-IL-1, and pro-IL-18. In the activation phase, NLRP3 recruits ASC, which then binds to pro-caspase-1, facilitating the assembly of the inflammasome. The oligomeric NLRP3 inflammasome enzymatically cleaves pro-IL-1 and pro-IL-18 into their active forms, IL-1 and IL-18, respectively. Additionally, caspase-1 cleaves GSDMD, forming pores that induce pyroptosis and the release of IL-1. Created with BioRender.com. ASC, apotosis-associated speck-like protein containing a CARD; DAMP, damage-associated molecular patterns; GSDMD, gasdermin D; IL, interleukin; NF-kB, nuclear factor k-light-chain enhancer of activated B cells; NLRP3, nucleotideoligomerization domain (NOD)- like receptor P3; PRRs, pattern recognition receptors; PAMP, pathogen-associated molecular patterns; TNF, tumor necrosis factor.