Abstract 15152: A Novel Nlrp3 Inflammasome Inhibitor Prevents Acute Pericarditis in an Experimental Mouse Model
Introduction: Acute pericarditis is characterized by inflammation of the pericardial layers. It responds to treatment with colchicine, an anti-inflammatory drug known to interfere with the formation of the NOD-Like receptor type 3 protein (NLRP3) inflammasome.
Hypothesis: Administration of a novel NLRP3 inflammasome inhibitor, derived from glyburide, decreases pericardial inflammation in a mouse model of acute pericarditis.
Methods: We induced acute pericarditis by injecting zymosan A, a yeast-derived activator of the NLRP3 inflammasome (1 mg in 50 μl of NaCl 0.9%), in the pericardial sac of CD-1 male mice, using a 30-gauge needle. An equivalent volume of vehicle was used in the control group. The NLRP3 inhibitor (NLRP3inh, 100 mg/kg, N=6) or colchicine (1000 or 100 μg/Kg, N=3) were administered by oral gavage once daily for 7 days in the zymosan-treated mice. Higher doses of colchicine (>1 mg/kg) were lethal. Transthoracic echocardiography was performed to evaluate pericardial effusion by measuring the dimension of the pericardial thickness and the effusion in M-mode and B-mode (Figure). Heart tissues were stained with hematoxylin/eosin to measure pericardial thickness, and immunofluorescence staining for the inflammasome scaffold protein ASC and cardiac actin, was performed in order to evaluate inflammasome formation within the pericardial layers.
Results: Intrapericardial instillation of zymosan produced a significantly greater pericardial effusion, thickening, and inflammation when compared with vehicle (all P<0.05, Figure). Administration of the NLRP3inh or colchicine significantly limited the intensity of pericardial inflammation as measured by the dimensions of pericardial effusion, thickening, and ASC staining, compared to untreated mice (Figure).
Conclusions: Inhibition of the NLRP3 inflammasome using a novel inhibitor significantly reduces pericardial inflammation in experimental acute pericarditis in the mouse.
Author Disclosures: A.G. Mauro: None. E. Mezzaroma: None. J.F. Torrado: None. S. Carbone: None. B.W. Van Tassell: None. A. Abbate: None. S. Toldo: None.
- © 2016 by American Heart Association, Inc.