Figure 2.

Hematopoietic-specific inactivation of Tet2 augments AF inducibility in Ldlr^−/− mice. A, Lethally irradiated Ldlr^−/− mice transplanted with bone marrow with hematopoietic-specific inactivation of Tet2 (Tet2KO) or WT controls and fed Western diet (WD) for 6 to 9 weeks. B, Representative tracing of pacing-induced AF, showing surface ECG, right atrial (RA) and right ventricle (RV) intracardiac electrograms. C, Hematopoieticspecific inactivation of Tet2 resulted in an increased number of mice inducible for AF (number of mice with AF/total mice in the group). D, Increased AF inducibility was seen in Tet2KO mice. Percentage reflects ratio of total number of provoked AF episodes to total programmed electrical provocations. E, Atrial effective refractory period (AERP) measured at a drivetrain of 100 ms, demonstrating shortening in Tet2KO recipients. F, Optically derived right atrial action potential duration at 90% repolarization (RA APD90). Representative optical action potential tracing to right. G, Relative atrial protein expression of Nlrp3, with representative blots below, showing >3-fold increase in Nlrp3 expression. Western blot quantification relative to vinculin loading control and then normalized. Statistical testing: Fisher exact test for C and D; 2-tailed Student t test for E through G. Mean (SD) shown for E and F. AF indicates atrial fibrillation; A.U., arbitrary units; KO, knockout; LDLR, low-density lipoprotein receptor; Nlrp3, NLR (NACHT, LRR [leucine rich repeat]) family pyrin domain containing protein 3; TET2, tet methylcystosine dioxygenase 2; and WT, wild-type.