CE-452774-1 NOX2 INHIBITION REDUCES AF IN DIET-INDUCED OBESE MICE BY REVERSING ATRIAL REMODELING CAUSED BY INCREASED ROS PRODUCTION

Diet induced obese (DIO) mice display both increased susceptibility to inducible atrial fibrillation (AF) and an overall increase in reactive oxygen species (ROS) production specific the cytosol mitochondria. NADPH oxidase 2 (NOX2), a major source of cytosolic ROS human atria, has been implicated ion channel remodeling leading AF independent obesity is significantly atria DIO mice. Although treatment with MitoTEMPO, mitochondrial antioxidant (MitoTEMPO) reduced burden mice, actual role NOX2 increasing context obesity-induced remains unclear. To test hypothesis that modulates AF, we used lean control Nox2-KO fed 60% for period 10 weeks (DIO Nox2 -KO mice) treated blocker, apocynin (DIO-Apocynin). Trans-esophageal rapid (TE) pacing echocardiography were look at changes phenotype heart function. Cellular electrophysiology (EP), immunohistochemistry, Western blotting, whole-cell patch clamping optical mapping studies performed study oxidative stress production. The average weight control, DIO, DIO-Apocynin, 31.70 ± 1.19 g, 38.18 3.848 43.96 7.584 39.93 4.99 g respectively. (Figure A) After TE pacing, DIO-Apocynin displayed 28.26 25.40 s 17.43 31.80 compared 167.3 168.9 B). Whole cell electrical show inhibition reverses E-F) fibrosis I-J) seen prolongs AP C-D) increases conduction velocity (CV) G-H) left atria. B) Also cells from expression protein SOD2 superoxide K-L) Thus, these results prove therapy targeting abrogated reversed burden. Our findings importance pathways manage patients obesity.