The NLRP3 inflammasome in acute myocardial infarction

Key Points

  • The inflammasome is a macromolecular structure in the cell responsible for sensing danger and triggering a local or systemic inflammatory response

  • Upon activation, the inflammasome produces large amounts of active cytokines (primarily IL-1β) for extracellular secretion, and those cytokines mediate the acute phase of an inflammatory response, such as fever

  • The most widely characterized inflammasome sensor in the heart is NACHT, LRR, and PYD domains-containing protein 3 (NLRP3), which is activated in response to noninfectious stimuli such as cell debris during acute myocardial infarction

  • Activation of the NLRP3 inflammasome triggers further myocardial damage indirectly through the release of IL-1β and directly through promotion of inflammatory cell death via pyroptosis

  • Experimental studies have shown that strategies inhibiting the activation of the NLRP3 inflammasome in the early reperfusion period after acute myocardial infarction reduce the overall size of the infarct and preserve normal cardiac function

  • IL-1 blockade can prevent the recurrence of acute myocardial infarction in patients who have experienced a previous event and might improve exercise capacity and cardiac function in patients with heart failure


The heart is extremely sensitive to ischaemic injury. During an acute myocardial infarction (AMI) event, the injury is initially caused by reduced blood supply to the tissues, which is then further exacerbated by an intense and highly specific inflammatory response that occurs during reperfusion. Numerous studies have highlighted the central role of the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome in this process. The inflammasome, an integral part of the innate immune system, is a macromolecular protein complex that finely regulates the activation of caspase 1 and the production and secretion of powerful pro-inflammatory cytokines such as IL-1β and IL-18. In this Review, we summarize evidence supporting the therapeutic value of NLRP3 inflammasome-targeted strategies in experimental models, and the data supporting the role of the NLRP3 inflammasome in AMI and its consequences on adverse cardiac remodelling, cytokine-mediated systolic dysfunction, and heart failure.

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Figure 1: NLRP3 inflammasome formation pathways.
Figure 2: Strategies to reduce infarct size by inhibiting the NLRP3 inflammasome in experimental animal models of myocardial ischaemia–reperfusion injury.
Figure 3: Mechanism of action of NLRP3 inhibitors tested in experimental models of acute myocardial infarction.
Figure 4: Window of opportunity for intervention using NLRP3 inhibitors in ischaemia–reperfusion injury.
Figure 5: Role of IL-1β in acute myocardial infarction.


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The authors are grateful to Salvatore Carbone (Virginia Commonwealth University, Richmond, USA) for critically reviewing the manuscript and to Charles Dinarello (University of Colorado Denver, USA) for mentorship and guidance in the field of IL-1 over the past 10 years. S.T. is supported by a grant from the Virginia Commonwealth University Center for Clinical & Translational Research, a VCU Commercialization Fund Award, and a Department of Internal Medicine Pilot Study Award. A.A. is supported by grants (HL121402 and HL136816) from the National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA.

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Both authors researched data for the article, discussed the content, wrote the manuscript, and reviewed and edited the manuscript before submission.

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Correspondence to Antonio Abbate.

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Competing interests

S.T. has received research grants from Olatec. A.A. has received research grants from Novartis and Swedish Orphan Biovitrum and has served as a scientific adviser to Olatec.

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Toldo, S., Abbate, A. The NLRP3 inflammasome in acute myocardial infarction. Nat Rev Cardiol 15, 203–214 (2018).

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