Compensatory mechanisms acting in dystrophin deficient hearts

Duchenne muscular dystrophy (DMD), the best‐known form of muscular dystrophy, is due to mutation on the chromosome X that prevents dystrophin production. Dystrophin is responsible for protecting sarcolemmal integrity, its absence turning striated muscle cells, skeletal and cardiac, more vulnerable to disruption and death. Despite the better knowledge on basic pathological mechanisms, there is no cure for DMD, patients usually dying due to muscle‐based breathing and heart problems. The compensatory mechanisms related to dystrophin deficiency are partially known. Subsarcolemmal expression of utrophin, a protein analogue to dystrophin, is a well‐known compensatory mechanism to dystrophin deficiency. mdx mice, an experimental model of DMD, present increased expression of utrophin, which would provide the compensation to dystrophin absence. This would explain the reason of an mdx mice life expectancy similar to that of WT controls. Considering that double‐knockout mdx:utr−/− mice can live up to 20 weeks of age, similarly to a human patient with both dystrophin and utrophin deficiency, other compensatory mechanisms should be working. This study demonstrates, for the first time, cardiac intercalated disc remodeling characterized by overexpression of adhesion molecules implicated in specialized mechanical and electrochemical structures, functioning as additional compensatory mechanisms in mdx mice.