Cardiac-specific deletion of alpha-E-catenin in mice led to progressive dilated cardiomyopathy, right ventricular defects, and striking susceptibility to ventricular free wall rupture after myocardial infarction.
Does cardiac-specific inactivation of alpha-E-catenin lead to cardiomyopathy and susceptibility to wall rupture in mice?
Ablation of alpha-E-catenin in cardiomyocytes disrupts the adherens junction, leading to dilated cardiomyopathy and increased susceptibility to ventricular wall rupture after myocardial stress.
BACKGROUND: alpha-E-catenin is a cell adhesion protein, located within the adherens junction, thought to be essential in directly linking the cadherin-based adhesion complex to the actin cytoskeleton. Although alpha-E-catenin is expressed in the adherens junction of the cardiomyocyte intercalated disc, and perturbations in its expression are observed in models of dilated cardiomyopathy, its role in the myocardium remains unknown. METHODS AND RESULTS: To determine the effects of alpha-E-catenin on cardiomyocyte ultrastructure and disease, we generated cardiac-specific alpha-E-catenin conditional knockout mice (alpha-E-cat cKO). alpha-E-cat cKO mice displayed progressive dilated cardiomyopathy and unique defects in the right ventricle. The effects on cardiac morphology/function in alpha-E-cat cKO mice were preceded by ultrastructural defects in the intercalated disc and complete loss of vinculin at the intercalated disc. alpha-E-cat cKO mice also revealed a striking susceptibility of the ventricular free wall to rupture after myocardial infarction. CONCLUSIONS: These results demonstrate a clear functional role for alpha-E-catenin in the cadherin/catenin/vinculin complex in the myocardium in vivo. Ablation of alpha-E-catenin within this complex leads to defects in cardiomyocyte structural integrity that result in unique forms of cardiomyopathy and predisposed susceptibility to death after myocardial stress. These studies further highlight the importance of studying the role of alpha-E-catenin in human cardiac injury and cardiomyopathy in the future.
Sheikh et al. (Tue,) conducted a other in Cardiomyopathy and myocardial infarction. Cardiac-specific alpha-E-catenin conditional knockout vs. Control mice was evaluated on Cardiac morphology/function, ultrastructural defects, and susceptibility to ventricular free wall rupture after myocardial infarction. Cardiac-specific deletion of alpha-E-catenin in mice led to progressive dilated cardiomyopathy, right ventricular defects, and striking susceptibility to ventricular free wall rupture after myocardial infarction.
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