NLR/inflammasome pathway in cardiovascular disorders: from pathogenesis to potential therapies

Abstract

The inflammasome is a multimeric protein complex that plays an essential role in the innate immune response by triggering the cleavage and activation of the proinflammatory cytokines interleukins (IL)-1 beta and IL-18. The dysregulation of NLRs and subsequent inflammasome activation has emerged under various pathologic conditions that contribute to the progression of heart failure, including pressure overload, acute or chronic overactivation of the sympathetic system, myocardial infarction, and diabetic cardiomyopathy. Our study unfolds by examining the pivotal role of the NLRP3 inflammasome in cardiac inflammation and fibrosis, exploring the intricate signalling pathways, including NLRs, involved in the initiation and progression of heart failure. Insights from preclinical and clinical studies indicate the use of potential therapeutic strategies targeting NLRs and the inflammasome to mitigate adverse cardiac outcomes. This review aims to consolidate existing knowledge, pinpoint gaps in our understanding, and propose directions for future research. This study may elucidate the function of NLRs/inflammasomes in heart failure and establishes a foundation for subsequent research focused on developing targeted therapeutics to alleviate inflammatory pathways associated with heart failure.