Mkk4 is a negative regulator of the transforming growth factor beta 1 signaling associated with atrial remodeling and arrhythmogenesis with age.

Background: Atrial fibrillation (AF), often associated with structural, fibrotic change in cardiac tissues involving regulatory signaling mediators, becomes increasingly common with age. In the present study, we explored the role of mitogen-activated protein kinase kinase 4 (Mkk4), a critical component of the stress-activated mitogen-activated protein kinase family, in age-associated AF.

Methods And Results: We developed a novel mouse model with a selective inactivation of atrial cardiomyocyte Mkk4 (Mkk4(ACKO)).