Impact of dystrophin deficiency on vascular smooth muscle cell

Duchenne Muscular Dystrophy (DMD) is a severe genetic disorder affecting skeletal and cardiac muscles, primarily in males. While much research has focused on these systems, the role of vascular smooth muscle cells (VSMCs) remains underexplored. This study examines how dystrophin deficiency alters VSMCs plasticity using mdx mice and DMD patient-derived iPSC VSMCs. Immunohistochemistry, Western blot, electron microscopy, and transcriptomic analyses revealed significant abnormalities. In mdx mice, abnormal vascular structure and vascular degeneration were observed. DMD VSMCs showed impaired maturation, reduced contractile protein expression, and disrupted mitochondrial dynamics, including excessive fission and reduced mitochondrial area. These cells also exhibited increased apoptosis under oxidative stress. Transcriptomic profiling identified dysregulated genes related to VSMC proliferation, differentiation, and vascular development, with transcription factors such as GADD45A, SOX9, TIA1, RBBP9, and FOXM1 implicated. Under stress, apoptotic pathways were notably upregulated. These findings suggest that dystrophin deficiency drives VSMC phenotype switching and mitochondrial dysfunction, contributing to vascular pathology in DMD. These findings highlight the importance of targeting vascular abnormalities in therapeutic strategies to slow disease progression.