NLRP3 Inflammasome as a Novel Player in Myocardial Infarction

Abstract

SummaryInfl ammasomes are multiple protein complexes that serve as molecular platforms to activate caspase-1 and regulate maturation of a potent proinfl ammatory cytokine, interleukin (IL)-1β, as well as proinfl ammatory cell death, pyroptosis. Although several types of infl ammasomes have been reported so far, recent investigations indicate that the NLRP3 infl ammasome recognizes non-microbial danger signals and leads to sterile infl ammatory responses in various disease conditions. Sterile infl ammatory responses are also implicated in the development of myocardial infarction (MI). In particular, IL-1β is an early and prominent mediator of infl ammatory responses in MI, suggesting the pathophysiologic role of NLRP3 infl ammasomes in MI. This review highlights the current state of knowledge regarding the role of NLRP3 infl ammasomes in MI. (Int Heart J 2014; 55: 101-105)

Letter by Mezzaroma, <i>et al</i> Regarding Article, “NLRP3 Inflammasome as a Therapeutic Target in Myocardial Infarction”

“…4) As pointed out in the review, the NLRP3 inflammasome is not only involved in the production of cytokines, but may directly participate in cardiomyocyte cell death through the activation of caspase-1. 1) We agree with the author that NLRP3 is a potentially valuable target for a therapeutic intervention. We want to report that we have recently developed a novel NLRP3 inhibitor effective both in vitro and in vivo.…”

“…The NLRP3 inflammasome is activated by several stimuli produced during tissue injury or stress and, following the interaction with the ASC and the proinflammatory enzyme caspase-1, induces production of the mature forms of the pro-inflammatory cytokines IL-1β and IL-18. 1) As evidenced in this review, the investigation on the role of the single components of the inflammasome has generated contradictory data, 1) however, the consensus is that the blockade of the NLRP3 inflammasome may be a valuable therapeutic target. Therefore, NLRP3 may be acting through two different mechanisms of inflammasome-mediated and inflammasome-independent myocardial damage.…”

“…Therefore, NLRP3 may be acting through two different mechanisms of inflammasome-mediated and inflammasome-independent myocardial damage. 1) Several pre-clinical studies have provided evidence that targeted IL-1 signaling blockade (with one exception) is a strategy to reduce ischemic injury to the heart.…”

Naoxintong attenuates Ischaemia/reperfusion Injury through inhibiting NLRP3 inflammasome activation

“…Increasing evidence also indicates that a sterile inflammatory response triggered by tissue damage is mediated through a multiple‐protein complex called the inflammasome 4, 5. It is known that nucleotide‐binding oligomerization domain‐Like Receptor with a Pyrin domain 3 (NLRP3) inflammasome are formed after myocardial I/R injury and the subsequent activation process could lead to the interleukin‐1β production 6, 7, which crucially contributes to cardiac ischaemia injury and post‐infarct remodelling.…”

Reply to Letter Regarding Article, “NLRP3 Inflammasome as a Therapeutic Target in Myocardial Infarction”

“…We thank Mezzaroma, et al for their interest in our review article, 1) which describes the critical role of NLRP3 inflammasomes in inflammatory responses and tissue remodeling after myocardial infarction (MI). Moreover, we congratulate them for developing a novel pharmacological inhibitor of NLRP3 inflammasomes.…”