摘要：SummaryDuchenne muscular dystrophy (DMD), caused by mutations in the dystrophin gene, is characterized by progressive muscle weakness. Even though DMD manifests first in skeletal muscle, heart failure is a major cause of death in late-stage DMD. To get insights into DMD-associated cardiomyopathy, we performed a proteome analysis of myocardium from a genetically engineered porcine DMD model resembling clinical and pathological hallmarks of human DMD. To capture DMD progression, samples from 2-day- and 3-month-old animals were analyzed. Dystrophin was absent in all DMD samples, and components of the dystrophin-associated protein complex were decreased, suggesting destabilization of the cardiomyocyte plasma membrane and impaired cellular signaling. Furthermore, abundance alterations of proteins known to be associated with human cardiomyopathy were observed. Compared with data from skeletal muscle, we found clear evidence that DMD progression in myocardium is not only slower than in skeletal muscle but also involves different biological and biochemical pathways.Graphical AbstractDisplay OmittedHighlights•Proteomics of myocardium from a genetically engineered DMD pig model was performed•The results indicate an arising inflammatory pathology in the myocardium of DMD pigs•Alterations of proteins known to be related to cardiomyopathy were found in DMD pigs•Proteome changes in DMD pigs markedly differ between myocardium and skeletal musclePathophysiology; Proteomics
