The selective NLRP3-inflammasome inhibitor MCC950 reduces infarct size and preserves cardiac function in a pig model of myocardial infarction

European Heart Journal

Volumn 38, Issue 11, 2017, Pages 828-836

  Van Hout, Gerardus P J ^a   Bosch, Lena ^a   Ellenbroek, Guilielmus H J M ^a   De Haan, Judith J ^a   Van Solinge, Wouter W ^a   Cooper, Matthew A ^b   Arslan, Fatih ^a   De Jager, Saskia C A ^a   Robertson, Avril A B ^b   Pasterkamp, Gerard ^a   Hoefer, Imo E ^a  

^a UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

^b UNIVERSITY OF QUEENSLAND   (Australia)

Author keywords

Cardiac function; Infarct size; Inflammasome; Inflammation; Inhibitor; Myocardial infarction

Indexed keywords

ANTIINFLAMMATORY AGENT; CRYOPYRIN; INFLAMMASOME; INTERLEUKIN 1BETA; MCC 950; PLACEBO; PROTEIN INHIBITOR; UNCLASSIFIED DRUG; BIOLOGICAL MARKER; FUSED HETEROCYCLIC RINGS; MCC-950; SULFONE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DOSE RESPONSE; DRUG DOSE COMPARISON; DRUG MEGADOSE; FEMALE; HEART FUNCTION; HEART INFARCTION; HEART INFARCTION SIZE; HEART LEFT VENTRICLE EJECTION FRACTION; HEART PROTECTION; LANDRACE PIG; LOW DRUG DOSE; NEUTROPHIL CHEMOTAXIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN CONTENT; THREE DIMENSIONAL ECHOCARDIOGRAPHY; TISSUE LEVEL; TREATMENT OUTCOME; ANIMAL; ANTAGONISTS AND INHIBITORS; BALLOON OCCLUSION; ECHOCARDIOGRAPHY; HEMODYNAMICS; METABOLISM; MONONUCLEAR CELL; PATHOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY; PIG; PROCEDURES; RANDOMIZATION;

ANIMALS; BALLOON OCCLUSION; BIOMARKERS; ECHOCARDIOGRAPHY; FEMALE; HEMODYNAMICS; HETEROCYCLIC COMPOUNDS, 4 OR MORE RINGS; INFLAMMASOMES; LEUKOCYTES, MONONUCLEAR; MYOCARDIAL INFARCTION; NLR FAMILY, PYRIN DOMAIN-CONTAINING 3 PROTEIN; RANDOM ALLOCATION; SULFONES; SWINE;

EID: 84994716083     PISSN: 0195668X     EISSN: 15229645     Source Type: Journal    
DOI: 10.1093/eurheartj/ehw247     Document Type: Article

References (36)

1. Steg PG, James SK, Atar D, Badano LP, Lundqvist CB, Borger MA, Di Mario C, Dickstein K, Ducrocq G, Fernandez-Aviles F, Gershlick AH, Giannuzzi P, Halvorsen S, Huber K, Juni P, Kastrati A, Knuuti J, Lenzen MJ, Mahaffey KW, Valgimigli M, Van'T Hof A, Widimsky P, Zahger D, Bax JJ, Baumgartner H, Ceconi C, Dean V, Deaton C, Fagard R, Funck-Brentano C, Hasdai D, Hoes A, Kirchhof P, Kolh P, McDonagh T, Moulin C, Popescu BA, Reiner Z, Sechtem U, Sirnes PA, Tendera M, Torbicki A, Vahanian A, Windecker S, Astin F, Aström-Olsson K, Budaj A, Clemmensen P, Collet JP, Fox KA, Fuat A, Gustiene O, Hamm CW, Kala P, Lancellotti P, Maggioni AP, Merkely B, Neumann FJ, Piepoli MF, Van de Werf F, Verheugt F, Wallentin L, Blömstrom-Lundqvist C, Borger MA, Di Mario C, Dickstein K, Ducrocq G, Fernandez-Aviles F, Gershlick AH, Giannuzzi P, Halvorsen S, Huber K, Juni P, Kastrati A, Knuuti J, Lenzen MJ, Mahaffey KW, Valgimigli M, van 't Hof A, Widimsky P, Zahger D. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2012;33: 2569-2619.
2. Bleumink GS, Knetsch AM, Sturkenboom MCJM, Straus SMJM, Hofman A, Deckers JW, Witteman JCM, Stricker BHC. Quantifying the heart failure epidemic: prevalence, incidence rate, lifetime risk and prognosis of heart failure-The Rotterdam Study. Eur Heart J 2004;25:1614-1619.
3. Arslan F, de Kleijn DP, Pasterkamp G. Innate immune signaling in cardiac ischemia. Nat Rev Cardiol 2011;8:292-300.
4. Timmers L, Pasterkamp G, De Hoog VC, Arslan F, Appelman Y, V De Kleijn DP. The innate immune response in reperfusedmyocardium. Cardiovasc Res 2012;94:276-283.
5. Sutton MG, Sharpe N. Left ventricular remodeling after myocardial infarction: pathophysiology and therapy. Circulation 2000;101:2981-2988.
6. Ibánẽz B, Heusch G, Ovize M, Van de Werf F. Evolving therapies for myocardial ischemia/reperfusion injury. J Am Coll Cardiol 2015;65:1454-1471.
7. Bujak M, Frangogiannis NG. The role of IL-1 in the pathogenesis of heart disease. Arch Immunol Ther Exp (Warsz) 2009;57:165-176.
8. Sims JE, Smith DE. The IL-1 family: regulators of immunity. Nat Rev Immunol. Nature Publishing Group; 2010;10:89-102.
9. Toldo S, Mezzaroma E, O'Brien L, Marchetti C, Seropian IM, Voelkel NF, Van Tassell BW, Dinarello CA, Abbate A. Interleukin-18 mediates interleukin-1-induced cardiac dysfunction. AJP Hear Circ Physiol 2014;306:H1025-H1031.
10. Blankenberg S, Luc G, Ducimetière P, Arveiler D, Ferrières J, Amouyel P, Evans A, Cambien F, Tiret L. Interleukin-18 and the risk of coronary heart disease in European Men: The Prospective Epidemiological Study of Myocardial Infarction (PRIME). Circulation 2003;108:2453-2459.
11. Hartford M, Wiklund O, Hultén LM, Persson A, Karlsson T, Herlitz J, Hulthe J, Caidahl K. Interleukin-18 as a predictor of future events in patients with acute coronary syndromes. Arterioscler Thromb Vasc Biol 2010;30:2039-2046.
12. Van Tassell BW, Raleigh JMV, Abbate A. Targeting interleukin-1 in heart failure and inflammatory heart disease. Curr Heart Fail Rep 2014;12:33-41.
13. Salloum FN, Chau V, Varma A, Hoke NN, Toldo S, Biondi-Zoccai GGL, Crea F, VetrovecGW, Abbate A. Anakinra in experimental acute myocardial infarction-does dosage or duration of treatment matter? Cardiovasc Drugs Ther 2009;23:129-135.
14. Abbate A, Salloum FN, Vecile E, Das A, Hoke NN, Straino S, Biondi-Zoccai GG, Houser JE, Qureshi IZ, Ownby ED, Gustini E, Biasucci LM, Severino A, Capogrossi MC, Vetrovec GW, Crea F, Baldi A, Kukreja RC, Dobrina A. Anakinra, a recombinant human interleukin-1 receptor antagonist, inhibits apoptosis in experimental acute myocardial infarction. Circulation 2008;117:2670-2683.
15. Venkatachalam K, Prabhu SD, Reddy VS, Boylston WH, Valente AJ, Chandrasekar B. Neutralization of interleukin-18 ameliorates ischemia/reperfusion-induced myocardial injury. J Biol Chem 2009;284:7853-7865.
16. Wang M, Tan J, Wang Y, Meldrum KK, Dinarello CA, Meldrum DR. IL-18 binding protein-expressing mesenchymal stem cells improve myocardial protection after ischemia or infarction. Proc Natl Acad Sci USA 2009;106:17499-17504.
17. Latz E, Xiao TS, Stutz A. Activation and regulation of the inflammasomes. Nat Rev Immunol 2013;13:397-411.
18. Zuurbier CJ, Jong WMC, Eerbeek O, Koeman A, Pulskens WP, Butter LM, Leemans JC, Hollmann MW. Deletion of the innate immune NLRP3 receptor abolishes cardiac ischemic preconditioning and is associated with decreased IL-6/STAT3 signaling. PLoS ONE 2012;7:e40643.
19. Sandanger O, Ranheim T, Vinge LE, Bliksøen M, Alfsnes K, Finsen AV, Dahl CP, Askevold ET, Florholmen G, Christensen G, Fitzgerald KA, Lien E, Valen G, Espevik T, Aukrust P, Yndestad A. The NLRP3 inflammasome is up-regulated in cardiac fibroblasts and mediates myocardial ischaemia-reperfusion injury. Cardiovasc Res 2013;99:164-174.
20. Mezzaroma E, Toldo S, Farkas D, Seropian IM, Van Tassell BW, Salloum FN, Kannan HR, Menna AC, Voelkel NF, Abbate A. The inflammasome promotes adverse cardiac remodeling following acute myocardial infarction in the mouse. Proc Natl Acad Sci USA 2011;108:19725-19730.
21. Kawaguchi M, Takahashi M, Hata T, Kashima Y, Usui F, Morimoto H, Izawa A, Takahashi Y, Masumoto J, Koyama J, Hongo M, Noda T, Nakayama J, Sagara J, Taniguchi S, Ikeda U. Inflammasome activation of cardiac fibroblasts is essential for myocardial ischemia/reperfusion injury. Circulation 2011;123:594-604.
22. Marchetti C, Chojnacki J, Toldo S, Mezzaroma E, Tranchida N, Rose SW, Federici M, Van Tassell BW, Zhang S, Abbate A. A novel pharmacologic inhibitor of the NLRP3 inflammasome limits myocardial injury after ischemia-reperfusion in the mouse. J Cardiovasc Pharmacol 2014;63:316-322.
23. Lecour S, Botker HE, Condorelli G, Davidson SM, Garcia-Dorado D, Engel FB, Ferdinandy P, Heusch G, Madonna R, Ovize M, Ruiz-Meana M, Schulz R, Sluijter JPG, Van Laake LW, Yellon DM, Hausenloy DJ. ESC Working Group Cellular Biology of the Heart: Position Paper: improving the preclinical assessment of novel cardioprotective therapies. Cardiovasc Res 2014;104:399-411.
24. Coll RC, Robertson AAB, Chae JJ, Higgins SC, Munõz-Planillo R, Inserra MC, Vetter I, Dungan LS, Monks BG, Stutz A, Croker DE, Butler MS, Haneklaus M, Sutton CE, Núnẽz G, Latz E, Kastner DL, Mills KHG, Masters SL, Schroder K, Cooper MA, O'Neill LAJ. A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nat Med 2015;21:248-255.
25. Grundmann S, Bode C, Moser M. Inflammasome activation in reperfusion injury: Friendly fire on myocardial infarction? Circulation 2011;123:574-576.
26. Takahashi M. NLRP3 inflammasome as a novel player in myocardial infarction. Int Heart J 2014;55:101-105.
27. O'brien LC, Mezzaroma E, Van Tassell BW, Marchetti C, Carbone S, Abbate A, Toldo S. Interleukin-18 as a therapeutic target in acute myocardial infarction and heart failure. Mol Med 2014;20:221-229.
28. Abbate A, Van Tassell BW, Biondi-Zoccai GGL. Blocking interleukin-1 as a novel therapeutic strategy for secondary prevention of cardiovascular events. BioDrugs 2012;26:217-233.
29. Seok J, Warren HS, Cuenca AG, Mindrinos MN, Baker HV, Xu W, Richards DR, McDonald-Smith GP, Gao H, Hennessy L, Finnerty CC, López CM, Honari S, Moore EE, Minei JP, Cuschieri J, Bankey PE, Johnson JL, Sperry J, Nathens AB, Billiar TR, West MA, Jeschke MG, Klein MB, Gamelli RL, Gibran NS, Brownstein BH, Miller-Graziano C, Calvano SE, Mason PH, Cobb JP, Rahme LG, Lowry SF, Maier RV, Moldawer LL, Herndon DN, Davis RW, Xiao W, Tompkins RG. Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc Natl Acad Sci USA 2013;110:3507-3512.
30. Gross GJ, Baker JE, Moore J, Falck JR, Nithipatikom K. Abdominal surgical incision induces remote preconditioning of trauma (RPCT) via activation of bradykinin receptors (BK2R) and the cytochrome P450 epoxygenase pathway in canine hearts. Cardiovasc Drugs Ther 2011;25:517-522.
31. Hausenloy DJ, Yellon DM. Myocardial ischemia-reperfusion injury: A neglected therapeutic target. J Clin Invest 2013;123:92-100.
32. Jansen of Lorkeers SJ, Eding JEC, Vesterinen HM, van der Spoel TIG, Sena ES, Duckers HJ, Doevendans PA, Macleod MR, Chamuleau SAJ. Similar effect of autologous and allogeneic cell therapy for ischemic heart disease: systematic review and meta-analysis of large animal studies. Circ Res 2014;116:80-86.
33. Jong WMC, Leemans JC, Weber NC, Juffermans NP, Schultz MJ, Hollmann MW, Zuurbier CJ. Nlrp3 plays no role in acute cardiac infarction due to low cardiac expression. Int J Cardiol 2014;177:41-43.
34. Mcmurray JJV, Adamopoulos S, Anker SD, Auricchio A, Böhm M, Dickstein K, Falk V, Filippatos G, Fonseca C, Gomez-Sanchez MA, Jaarsma T, Kober L, Lip GYH, Maggioni AP, Parkhomenko A, Pieske BM, Popescu BA, Ronnevik PK, Rutten FH, Schwitter J, Seferovic P, Stepinska J, Trindade PT, Voors AA, Zannad F, Zeiher A, Bax JJ, Baumgartner H, Ceconi C, Dean V, Deaton C, Fagard R, Funck-Brentano C, Hasdai D, Hoes A, Kirchhof P, Knuuti J, Kolh P, Mcdonagh T, Moulin C, Reiner Z, Sechtem U, Sirnes PA, Tendera M, Torbicki A, Vahanian A, Windecker S, Bonet LA, Avraamides P, Ben Lamin HA, Brignole M, Coca A, Cowburn P, Dargie H, Elliott P, Flachskampf FA, Guida GF, Hardman S, Iung B, Merkely B, Mueller C, Nanas JN, Nielsen OW, Orn S, Parissis JT, Ponikowski P. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012. Eur J Heart Fail 2012;14:803-869.
35. Weinheimer-Haus EM, Mirza RE, Koh TJ. Nod-like receptor protein-3 inflammasome plays an important role during early stages of wound healing. PLoS ONE 2015;10:e0119106.
36. Holmes JW, Yamashita H, Waldman LK, Covell JW. Scar remodeling and transmural deformation after infarction in the pig. Circulation 1994;90:411-420.