Emerging Roles of Dystroglycan in Cardiac Remodeling, Fibrosis, and Heart Failure

The dystrophin–glycoprotein complex (DGC) is a structural and signaling network of cardiac muscle. It connects the extracellular matrix to the intracellular cytoskeleton. Dystroglycan, a component of the DGC, plays an essential role in maintaining the integrity of the sarcolemma of cardiac muscle. It contributes to sarcolemma stability, force transmission, mechanotransduction, calcium homeostasis, and cardiomyocyte survival. While the role of dystroglycan signaling is well established in many inherited disorders such as Duchenne muscular dystrophy, it is less studied in acquired heart failure with reduced ejection fraction (HFrEF). Emerging evidence suggests that dystroglycan remodeling may also occur in HFrEF. This review critically analyzes dystroglycan signaling in healthy and failing hearts, with particular emphasis on its emerging role in acquired HFrEF, including cardiac remodeling and fibrosis.