Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

The NLRP3 inflammasome in acute myocardial infarction

Nature Reviews Cardiology volume 15, pages 203–214 (2018)Cite this article

Subjects

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

Abstract

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

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.

Similar content being viewed by others

References

  1. Anderson, J. L. & Morrow, D. A. Acute myocardial infarction. N. Engl. J. Med. 376, 2053–2064 (2017).

    Article  CAS  PubMed  Google Scholar 

  2. Eapen, Z. J. et al. Defining heart failure end points in ST-segment elevation myocardial infarction trials: integrating past experiences to chart a path forward. Circ. Cardiovasc. Qual. Outcomes 5, 594–600 (2012).

    Article  PubMed  Google Scholar 

  3. Seropian, I. M., Toldo, S., van Tassell, B. W. & Abbate, A. Anti-inflammatory strategies for ventricular remodeling following ST-segment elevation acute myocardial infarction. J. Am. Coll. Cardiol. 63, 1593–1603 (2014).

    Article  CAS  PubMed  Google Scholar 

  4. Westman, P. C. et al. Inflammation as a driver of adverse left ventricular remodeling after acute myocardial infarction. J. Am. Coll. Cardiol. 67, 2050–2060 (2016).

    Article  PubMed  Google Scholar 

  5. Gao, X. M., White, D. A., Dart, A. M. & Du, X. J. Post-infarct cardiac rupture: recent insights on pathogenesis and therapeutic interventions. Pharmacol. Ther. 134, 156–179 (2012).

    Article  CAS  PubMed  Google Scholar 

  6. Abbate, A. et al. Alterations in the interleukin-1/interleukin-1 receptor antagonist balance modulate cardiac remodeling following myocardial infarction in the mouse. PLoS ONE 6, e27923 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Savvatis, K. et al. Interleukin-23 deficiency leads to impaired wound healing and adverse prognosis after myocardial infarction. Circ. Heart Fail. 7, 161–171 (2014).

    Article  CAS  PubMed  Google Scholar 

  8. Toldo, S. et al. The inflammasome in myocardial injury and cardiac remodeling. Antioxid. Redox Signal. 22, 1146–1161 (2015).

    Article  CAS  PubMed  Google Scholar 

  9. Sutterwala, F. S., Haasken, S. & Cassel, S. L. Mechanism of NLRP3 inflammasome activation. Ann. NY Acad. Sci. 1319, 82–95 (2014).

    Article  CAS  PubMed  Google Scholar 

  10. Mezzaroma, E. et al. The inflammasome promotes adverse cardiac remodeling following acute myocardial infarction in the mouse. Proc. Natl Acad. Sci. USA 108, 19725–19730 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Lu, A. et al. Unified polymerization mechanism for the assembly of ASC-dependent inflammasomes. Cell 156, 1193–1206 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Dinarello, C. A. Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood 117, 3720–3732 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Westermann, D. et al. Cardioprotective and anti-inflammatory effects of interleukin converting enzyme inhibition in experimental diabetic cardiomyopathy. Diabetes 56, 1834–1841 (2007).

    Article  CAS  PubMed  Google Scholar 

  14. Rider, P., Carmi, Y., Voronov, E. & Apte, R. N. Interleukin-1α. Semin. Immunol. 25, 430–438 (2013).

    Article  CAS  PubMed  Google Scholar 

  15. Gross, O. et al. Inflammasome activators induce interleukin-1α secretion via distinct pathways with differential requirement for the protease function of caspase-1. Immunity 36, 388–400 (2012).

    Article  CAS  PubMed  Google Scholar 

  16. Liu, X. et al. Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores. Nature 535, 153–158 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Shao, W., Yeretssian, G., Doiron, K., Hussain, S. N. & Saleh, M. The caspase-1 digestome identifies the glycolysis pathway as a target during infection and septic shock. J. Biol. Chem. 282, 36321–36329 (2007).

    Article  CAS  PubMed  Google Scholar 

  18. Toldo, S. et al. Independent roles of the priming and the triggering of the NLRP3 inflammasome in the heart. Cardiovasc. Res. 105, 203–212 (2015).

    Article  CAS  PubMed  Google Scholar 

  19. Kawaguchi, M. et al. Inflammasome activation of cardiac fibroblasts is essential for myocardial ischemia/reperfusion injury. Circulation 123, 594–604 (2011).

    Article  CAS  PubMed  Google Scholar 

  20. Liu, A., Gao, X., Zhang, Q. & Cui, L. Cathepsin B inhibition attenuates cardiac dysfunction and remodeling following myocardial infarction by inhibiting the NLRP3 pathway. Mol. Med. Rep. 8, 361–366 (2013).

    Article  PubMed  Google Scholar 

  21. He, Y., Zeng, M. Y., Yang, D., Motro, B. & Núñez, G. NEK7 is an essential mediator of NLRP3 activation downstream of potassium efflux. Nature 530, 354–357 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Liu, Y. et al. TXNIP mediates NLRP3 inflammasome activation in cardiac microvascular endothelial cells as a novel mechanism in myocardial ischemia/reperfusion injury. Basic Res. Cardiol. 109, 415 (2014).

    Article  PubMed  CAS  Google Scholar 

  23. Ito, M. et al. Bruton's tyrosine kinase is essential for NLRP3 inflammasome activation and contributes to ischaemic brain injury. Nat. Commun. 6, 7360 (2015).

    Article  PubMed  Google Scholar 

  24. Starkov, A. A. The role of mitochondria in reactive oxygen species metabolism and signaling. Ann. NY Acad. Sci. 1147, 37–52 (2008).

    Article  CAS  PubMed  Google Scholar 

  25. Kim, J. S., He, L., Qian, T. & Lemasters, J. J. Role of the mitochondrial permeability transition in apoptotic and necrotic death after ischemia/reperfusion injury to hepatocytes. Curr. Mol. Med. 3, 527–535 (2003).

    Article  CAS  PubMed  Google Scholar 

  26. Zhou, R., Yazdi, A. S., Menu, P. & Tschopp, J. A role for mitochondria in NLRP3 inflammasome activation. Nature 469, 221–225 (2011).

    Article  CAS  PubMed  Google Scholar 

  27. Sadatomi, D. et al. Mitochondrial function is required for extracellular ATP-induced NLRP3 inflammasome activation. J. Biochem. 161, 503–512 (2017).

    CAS  PubMed  Google Scholar 

  28. Sun, Q., Fan, J., Billiar, T. R. & Scott, M. J. Inflammasome and autophagy regulation — a two-way street. Mol. Med. http://dx.doi.org/10.2119/molmed.2017.00077 (2017).

  29. Park, S. et al. Defective mitochondrial fission augments NLRP3 inflammasome activation. Sci. Rep. 5, 15489 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Mills, E. L., Kelly, B., O'Neill, L. A. J. Mitochondria are the powerhouses of immunity. Nat. Immunol. 18, 488–498 (2017).

    Article  CAS  PubMed  Google Scholar 

  31. Iyer, S. S. et al. Mitochondrial cardiolipin is required for Nlrp3 inflammasome activation. Immunity 39, 311–323 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Shi, C. S. et al. Activation of autophagy by inflammatory signals limits IL-1β production by targeting ubiquitinated inflammasomes for destruction. Nat. Immunol. 13, 255–263 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Wu, X. et al. Impaired autophagy contributes to adverse cardiac remodeling in acute myocardial infarction. PLoS ONE 9, e112891 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Netea, M. G. et al. Differential requirement for the activation of the inflammasome for processing and release of IL-1β in monocytes and macrophages. Blood 113, 2324–2335 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Mezzaroma, E., Toldo, S. & Abbate, A. Role of NLRP3 (cryopyrin) in acute myocardial infarction. Cardiovasc. Res. 99, 225–226 (2013).

    Article  CAS  PubMed  Google Scholar 

  36. Wang, L., Qu, P., Zhao, J. & Chang, Y. NLRP3 and downstream cytokine expression elevated in the monocytes of patients with coronary artery disease. Arch. Med. Sci. 10, 791–800 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Toldo, S. et al. Inhibition of the NLRP3 inflammasome limits the inflammatory injury following myocardial ischemia-reperfusion in the mouse. Int. J. Cardiol. 209, 215–220 (2016).

    Article  PubMed  Google Scholar 

  38. Sandanger, Ø. et al. NLRP3 inflammasome activation during myocardial ischemia reperfusion is cardioprotective. Biochem. Biophys. Res. Commun. 469, 1012–1020 (2016).

    Article  CAS  PubMed  Google Scholar 

  39. Marchetti, C. et al. A novel pharmacologic inhibitor of the NLRP3 inflammasome limits myocardial injury after ischemia-reperfusion in the mouse. J. Cardiovasc. Pharmacol. 63, 316–322 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Mastrocola, R. et al. Pharmacological inhibition of NLRP3 inflammasome attenuates myocardial ischemia/reperfusion injury by activation of RISK and mitochondrial pathways. Oxid. Med. Cell. Longev. 2016, 5271251 (2016).

    PubMed  PubMed Central  Google Scholar 

  41. Takahashi, M. NLRP3 inflammasome as a novel player in myocardial infarction. Int. Heart J. 55, 101–105 (2014).

    Article  CAS  PubMed  Google Scholar 

  42. Mezzaroma, E., Marchetti, C. & Toldo, S. Letter by Mezzaroma, et al regarding article, “NLRP3 inflammasome as a therapeutic target in myocardial infarction”. Int. Heart J. 55, 379 (2014).

    Article  PubMed  Google Scholar 

  43. Li, X. et al. NOD2 deficiency protects against cardiac remodeling after myocardial infarction in mice. Cell. Physiol. Biochem. 32, 1857–1866 (2013).

    Article  CAS  PubMed  Google Scholar 

  44. Sandanger, Ø. et al. The NLRP3 inflammasome is up-regulated in cardiac fibroblasts and mediates myocardial ischaemia-reperfusion injury. Cardiovasc. Res. 99, 164–174 (2013).

    Article  CAS  PubMed  Google Scholar 

  45. Jong, W. M. et al. Nlrp3 plays no role in acute cardiac infarction due to low cardiac expression. Int. J. Cardiol. 177, 41–43 (2014).

    Article  PubMed  Google Scholar 

  46. Lamkanfi, M. et al. Glyburide inhibits the cryopyrin/Nalp3 inflammasome. J. Cell Biol. 187, 61–70 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Marchetti, C. et al. Pharmacologic inhibition of the NLRP3 inflammasome preserves cardiac function after ischemic and nonischemic injury in the mouse. J. Cardiovasc. Pharmacol. 66, 1–8 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Marchetti, C., Swartzwelter, B., Koenders, M., Dinarello, C. A. & Joosten, L. A. OP0090 The human safe NLRP3 inflammasome inhibitor OLT1177 suppresses joint inflammation in murine models of experimental arthritis. Ann. Rheum. Dis. 76, 89 (2017).

    Google Scholar 

  49. OLATEC Lead compound. OLATEC http://www.olatec.com/lead-compound.html (2017).

  50. Juliana, C. et al. Anti-inflammatory compounds parthenolide and Bay 11–7082 are direct inhibitors of the inflammasome. J. Biol. Chem. 285, 9792–9802 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Kim, Y. S. et al. BAY 11–7082, a nuclear factor-κB inhibitor, reduces inflammation and apoptosis in a rat cardiac ischemia-reperfusion injury model. Int. Heart J. 51, 348–353 (2010).

    Article  CAS  PubMed  Google Scholar 

  52. Cocco, M. et al. Design, synthesis, and evaluation of acrylamide derivatives as direct NLRP3 inflammasome inhibitors. ChemMedChem. 11, 1790–1803 (2016).

    Article  CAS  PubMed  Google Scholar 

  53. Coll, R. C. et al. A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nat. Med. 21, 248–255 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. van Hout, G. P. et al. The selective NLRP3-inflammasome inhibitor MCC950 reduces infarct size and preserves cardiac function in a pig model of myocardial infarction. Eur. Heart J. 38, 828–836 (2017).

    CAS  PubMed  Google Scholar 

  55. Mauro, A. G., Thurber, C. & Abbate, A. Colchicine in acute myocardial infarction: “teaching new tricks to an old dog”. Transl Med. 5, e133 (2015).

    Google Scholar 

  56. Leung, Y. Y., Yao Hui, L. L. & Kraus, V. B. Colchicine — update on mechanisms of action and therapeutic uses. Semin. Arthritis Rheum. 45, 341–350 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Misawa, T. et al. Microtubule-driven spatial arrangement of mitochondria promotes activation of the NLRP3 inflammasome. Nat. Immunol. 14, 454–460 (2013).

    Article  CAS  PubMed  Google Scholar 

  58. Fujisue, K. et al. Colchicine improves survival, left ventricular remodeling, and chronic cardiac function after acute myocardial infarction. Circ. J. 81, 1174–1182 (2017).

    Article  CAS  PubMed  Google Scholar 

  59. Toldo, S., Marchetti, C. & Abbate, A. Re. “NLRP3 inflammasome activation during myocardial ischemia reperfusion is cardioprotective”. Biochem. Biophys. Res. Commun. 470, 811–812 (2016).

    Article  CAS  PubMed  Google Scholar 

  60. Sager, H. B. et al. Targeting interleukin-1β reduces leukocyte production after acute myocardial infarction. Circulation 132, 1880–1890 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. van Tassell, B. W., Toldo, S., Mezzaroma, E. & Abbate, A. Targeting interleukin-1 in heart disease. Circulation 128, 1910–1923 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  62. Abbate, A. et al. Anakinra a recombinant human interleukin-1 receptor antagonist, inhibits apoptosis in experimental acute myocardial infarction. Circulation 117, 2670–2683 (2008).

    Article  CAS  PubMed  Google Scholar 

  63. Toldo, S. et al. Interleukin-1β blockade improves cardiac remodelling after myocardial infarction without interrupting the inflammasome in the mouse. Exp. Physiol. 98, 734–745 (2013).

    Article  CAS  PubMed  Google Scholar 

  64. Toldo, S. et al. Interleukin-1β blockade improves left ventricular systolic/diastolic function and restores contractility reserve in severe ischemic cardiomyopathy in the mouse. J. Cardiovasc. Pharmacol. 64, 1–6 (2014).

    Article  CAS  PubMed  Google Scholar 

  65. Lugrin, J. et al. Cutting edge: IL-1α is a crucial danger signal triggering acute myocardial inflammation during myocardial infarction. J. Immunol. 194, 499–503 (2015).

    Article  CAS  PubMed  Google Scholar 

  66. Mauro, A. G. et al. Reduction of myocardial ischemia-reperfusion injury by inhibiting interleukin-1 alpha. J. Cardiovasc. Pharmacol. 69, 156–160 (2017).

    Article  CAS  PubMed  Google Scholar 

  67. O'Brien, L. C. et al. Interleukin-18 as a therapeutic target in acute myocardial infarction and heart failure. Mol. Med. 20, 221–229 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Pomerantz, B. J., Reznikov, L. L., Harken, A. H. & Dinarello, C. A. Inhibition of caspase 1 reduces human myocardial ischemic dysfunction via inhibition of IL-18 and IL-1β. Proc. Natl Acad. Sci. USA 98, 2871–2876 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Venkatachalam, K. et al. Neutralization of interleukin-18 ameliorates ischemia/reperfusion-induced myocardial injury. J. Biol. Chem. 284, 7853–7865 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Gu, H. et al. The protective role of interleukin-18 binding protein in a murine model of cardiac ischemia/reperfusion injury. Transpl. Int. 28, 1436–1444 (2015).

    Article  CAS  PubMed  Google Scholar 

  71. Pörksen, G. et al. Periodic fever, mild arthralgias, and reversible moderate and severe organ inflammation associated with the V198M mutation in the CIAS1 gene in three German patients — expanding phenotype of CIAS1 related autoinflammatory syndrome. Eur. J. Haematol. 73, 123–127 (2004).

    Article  PubMed  Google Scholar 

  72. Kumar, A. et al. Tumor necrosis factor alpha and interleukin 1beta are responsible for in vitro myocardial cell depression induced by human septic shock serum. J. Exp. Med. 183, 949–958 (1996).

    Article  CAS  PubMed  Google Scholar 

  73. Van Tassell, B. W. et al. Enhanced interleukin-1 activity contributes to exercise intolerance in patients with systolic heart failure. PLoS ONE 7, e33438 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Van Tassell, B. W., Seropian, I. M., Toldo, S., Mezzaroma, E. & Abbate, A. Interleukin-1β induces a reversible cardiomyopathy in the mouse. Inflamm Res. 62, 637–640 (2013).

    Article  CAS  PubMed  Google Scholar 

  75. Zhang, W. et al. Cardiac fibroblasts contribute to myocardial dysfunction in mice with sepsis: the role of NLRP3 inflammasome activation. PLoS ONE 9, e107639 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Bracey, N. A. et al. The Nlrp3 inflammasome promotes myocardial dysfunction in structural cardiomyopathy through interleukin-1β. Exp. Physiol. 98, 462–472 (2013).

    Article  CAS  PubMed  Google Scholar 

  77. Abbate, A. The heart on fire: inflammasome and cardiomyopathy. Exp. Physiol. 98, 385 (2013).

    Article  CAS  PubMed  Google Scholar 

  78. Wang, Y., Gao, B. & Xiong, S. Involvement of NLRP3 inflammasome in CVB3-induced viral myocarditis. Am. J. Physiol. Heart Circ. Physiol. 307, H1438–H1447 (2014).

    Article  CAS  PubMed  Google Scholar 

  79. Li, R. et al. Triptolide attenuates pressure overload-induced myocardial remodeling in mice via the inhibition of NLRP3 inflammasome expression. Biochem. Biophys. Res. Commun. 485, 69–75 (2017).

    Article  CAS  PubMed  Google Scholar 

  80. Seropian, I. M., Sonnino, C., Van Tassell, B. W., Biasucci, L. M. & Abbate, A. Inflammatory markers in ST-elevation acute myocardial infarction. Eur. Heart J. Acute Cardiovasc. Care 5, 382–395 (2016).

    Article  PubMed  Google Scholar 

  81. Deftereos, S. et al. Anti-inflammatory treatment with colchicine in acute myocardial infarction: a pilot study. Circulation 132, 1395–1403 (2015).

    Article  CAS  PubMed  Google Scholar 

  82. Nidorf, S. M., Eikelboom, J. W., Budgeon, C. A. & Thompson, P. L. Low-dose colchicine for secondary prevention of cardiovascular disease. J. Am. Coll. Cardiol. 61, 404–410 (2013).

    Article  CAS  PubMed  Google Scholar 

  83. Abbate, A. et al. Interleukin-1 blockade with anakinra to prevent adverse cardiac remodeling after acute myocardial infarction (Virginia Commonwealth University Anakinra Remodeling Trial [VCU-ART] Pilot study). Am. J. Cardiol. 105, 1371–1377 (2010).

    Article  CAS  PubMed  Google Scholar 

  84. Abbate, A. et al. Effects of interleukin-1 blockade with anakinra on adverse cardiac remodeling and heart failure after acute myocardial infarction [from the Virginia Commonwealth University-Anakinra Remodeling Trial (2) (VCU-ART2) pilot study]. Am. J. Cardiol. 111, 1394–1400 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Abbate, A. et al. Comparative safety of Interleukin-1 blockade with anakinra in patients with ST-segment elevation acute myocardial infarction (from the VCU-ART and VCU-ART2 pilot studies). Am. J. Cardiol. 115, 288–292 (2015).

    Article  CAS  PubMed  Google Scholar 

  86. US National Library of Medicine. ClinicalTrials.gov https://www.clinicaltrials.gov/ct2/show/NCT01950299 (2017).

  87. Morton, A. C. et al. The effect of interleukin-1 receptor antagonist therapy on markers of inflammation in non-ST elevation acute coronary syndromes: the MRC-ILA Heart Study. Eur. Heart J. 36, 377–384 (2015).

    Article  CAS  PubMed  Google Scholar 

  88. Abbate, A. & Dinarello, C. A. Anti-inflammatory therapies in acute coronary syndromes: is IL-1 blockade a solution? Eur. Heart J. 36, 337–339 (2015).

    Article  PubMed  Google Scholar 

  89. Van Tassell, B. W. et al. Effects of interleukin-1 blockade with anakinra on aerobic exercise capacity in patients with heart failure and preserved ejection fraction (from the D-HART pilot study). Am. J. Cardiol. 113, 321–327 (2014).

    Article  CAS  PubMed  Google Scholar 

  90. Van Tassell, B. W. et al. Interleukin-1 blockade in acute decompensated heart failure: a randomized, double-blinded, placebo-controlled pilot study. J. Cardiovasc. Pharmacol. 67, 544–551 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Van Tassell, B. et al. Interleukin-1 blockade in recently decompensated systolic heart failure: results from the REcently Decompensated Heart failure Anakinra Response trial (REDHART). Circ. Heart Fail. (in press).

  92. Van Tassell, B. et al. Interleukin-1 blockade in heart failure with preserved ejection fraction: rationale and design of the Diastolic Heart failure Anakinra Response Trial 2 (DHART2). Clin. Cardiol. 40, 626–632 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  93. ILARIS. Learn how prescription ILARIS may help. ILARIS http://www.ilaris.com/index.jsp (2017).

  94. Ridker, P. M., Thuren, T., Zalewski, A. & Libby, P. Interleukin-1β inhibition and the prevention of recurrent cardiovascular events: rationale and design of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS). Am. Heart J. 162, 597–605 (2011).

    Article  CAS  PubMed  Google Scholar 

  95. Ridker, P. M. et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N. Engl. J. Med. 377, 1119–1131 (2017).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

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.

Author information

Authors and Affiliations

  1. Pauley Heart Center, Sanger Hall, 1201 East Marshall Street, Richmond, 23298, Virginia, USA

    Stefano Toldo & Antonio Abbate

  2. VCU Johnson Center for Critical Care and Pulmonary Research, Molecular Medicine Research Building, 1220 East Broad Street, Richmond, 23298, Virginia, USA

    Stefano Toldo & Antonio Abbate

  3. Division of Cardiothoracic Surgery, Sanger Hall, 1201 East Marshall Street, Richmond, 23298, Virginia, USA

    Stefano Toldo

Authors
  1. Stefano Toldo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Antonio Abbate
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

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

Corresponding author

Correspondence to Antonio Abbate.

Ethics declarations

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.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Toldo, S., Abbate, A. The NLRP3 inflammasome in acute myocardial infarction. Nat Rev Cardiol 15, 203–214 (2018). https://doi.org/10.1038/nrcardio.2017.161

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrcardio.2017.161

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing