Abstract 16702: Mitochondrial Mediated NLRP3 Inflammasome Promotes Cardiomyocyte Death

Introduction: Elevated level of serum homocysteine (Hcy) has been identified as a risk factor for accelerating progression of cardiovascular disease. The underlying mechanism by which NLRP3 inflammasomal activation accelerates cardiomyocyte death through damaged mitochondrial is unclear. Methods and Results: Acute myocardial infarction (AMI) procedure was performed on hCBS/mcbs knockout mice at the age of 10weeks. Severe HHcy remarkably aggravated infarction size, cardiomyocyte area, and interstitial fibrosis 6 weeks after MI from 22.7 ± 4.3%, 340 ± 54μm2, 13.9 ± 1.9% in control mice (Hcy, 7-10μM) to 33.6 ± 6.5%, 485 ± 65μm2, 26 ± 4.5%, respectively, (P=0.035, P= 0.041, P=0.002). Increased LV cavity dilatation and dysfunction were more significant as compared with control mice by echocardiography (5.9 ± 0.2 vs. 4.2 ± 0.4mm, P=0.039; LV ejection fraction, 22.6 ± 3.9% vs. 36.8 ± 4.0%, P=0.011). Cardiomyocyte apoptosis and ROS production were increased in post-MI HHcy mice as well. Cleavaged IL-1 β and caspa...