Targeted Cardiac Overexpression of A20 Improves Left Ventricular Performance and Reduces Compensatory Hypertrophy After Myocardial Infarction

Background— A20 was originally characterized as a tumor necrosis factor–inducible gene in human umbilical vein endothelial cells. As an inhibitor of nuclear factor-κB signaling, A20 protects against apoptosis, inflammation, and cardiac hypertrophy. In the present study, we tested the hypothesis that cardiac-specific overexpression of A20 could protect the heart from myocardial infarction. Methods and Results— We investigated the role of constitutive human A20 expression in acute myocardial infarction using a transgenic model. Transgenic mice containing the human A20 gene under the control of the α-myosin heavy chain promoter were constructed. Myocardial infarction was produced by coronary ligation in A20 transgenic mice and control animals. The extent of infarction was then quantified by 2-dimensional and M-mode echocardiography and by molecular and pathological analyses of heart samples in infarct and remote heart regions 7 days after myocardial infarction. Constitutive overexpression of A20 in the murin...