Abstract 15506: Inhibition of the NLRP3 Inflammasome Limits the Inflammatory Injury Following Myocardial Ischemia-reperfusion in the Mouse
Introduction: Acute myocardial infarction (AMI) initiates as a result of severe ischemia, and while reperfusion relieves ischemic injury, limiting the overall infarct size (IS), it also triggers a secondary ischemia-independent myocardial injury occurs contributing to the final IS.
Hypothesis: We hypothesize that inhibition of the Nod-like Receptor Protein-3 (NLRP3) inflammasome limits the progression of IS following myocardial ischemia/reperfusion (I/R).
Methods: Adult CD1 male mice were subjected to transient ligation the left coronary artery for 30 minutes followed by reperfusion (N=3-6 per each group). IS was measured by triphenyl tetrazolium chloride (TTC) staining method at 1, 3 and 24 hours, and with serum cardiac troponin I (cTnI) levels 24 hours after surgery. Myocardial NLPR3 expression was quantified at 3, 6 and 24 hours of reperfusion. A novel pharmacologic NLRP3 inhibitor (NLRP3inh) or vehicle were administrated intraperitoneally at time of reperfusion, or with a delay of 1 or 3 hours.
Results: IS measured at TTC was significantly larger at 24 hours (43±4% of the area at risk) vs 3 hours (30±5%) and 1 hour (11±2%, P<0.001 for trend). NLRP3 myocardial expression was also significantly increased at 24 hours (1,097±382% of sham, P<0.001) and 6 hours (928±380%, P<0.001) vs 3 hours (111±15%). When compared with vehicle, the NLRP3inh given at reperfusion did not significantly reduce IS at 3 hours, while it significantly reduced IS at 24 hours (Figure). Administration of the NLRP3inh 1 hour after reperfusion significantly reduced IS at 24 hours, while it did not when given with a delay of 3 hours (Figure).
Conclusions: Inhibition of the NLRP3 inflammasome within 1 hour of reperfusion limits the secondary inflammatory injury following myocardial ischemia-reperfusion.
Author Disclosures: S. Toldo: None. C. Marchetti: None. A.G. Mauro: None. E. Mezzaroma: None. S. Carbone: None. S. Zhang: None. F. Salloum: None. B.W. Van Tassell: None. A. Abbate: None.
- © 2015 by American Heart Association, Inc.