Dystrophin-associated protein complex and heart failure

Dystrophin is a member of the dystrophin-associated protein complex that includes the α and β forms of dystroglycan and the α, β, γ, and δ forms of sarcoglycans (figure). α-dystroglycan is extracellular, linking laminin-2 with transmembrane β-dystroglycan. Intracellularly the C-terminus of dystrophin links to γ-dystroglycan and the N-terminus to γ-actin and talin, connecting the extra cellular matrix with the cytoskeleton. Molecular remodelling of dystrophin in patients with end-stage cardiomyopathies and reversal in patients on assistance-device therapyDystrophin remodelling is a useful indicator of left-ventricular function in patients with dilated and ischaemic cardiomyopathy. Our results lend support to the hypothesis that changes in cytoskeletal proteins and, in particular, dystrophin might provide a final common pathway for contractile dysfunction in heart failure and these changes might be reversible by reduction of mechanical stress. Full-Text PDF