Sahil Kamat

Duchenne muscle dystrophy (DMD) is a genetic disease that leads to fibrosis and necrosis in the striated muscle of humans. Mice are commonly used as model organisms to study the disease pathogenesis. Here, we will utilize the mdx (dystrophic), the DBko (dystrobrevin-knockout), and the C06 (wild-type) mouse. Previous studies have indicated that DBko and mdx mice experience similar injury levels 30 hours post isoproterenol injection. In contrast, C06 mice demonstrate minimal cardiac damage, and there appears to be a median decrease in lesional percent injury 1-week post-injection as the lesional areas become fibrotic across all genotypes. However, the heart’s response and recovery from injury are unknown. Our pilot study shows a positive correlation between the extent of cardiac injury and high-level protein synthesis across all genotypes, suggesting a multi-cellular response to cardiac injury. Interestingly, most high-level protein synthesis does not occur adjacent to lesional areas but in remote areas, away from the lesions. Furthermore, we show that immune cells and cardiac myocytes play a prevalent role in responding to cardiac injury across all genotypes. We also show no genotype-specificity regarding low-level protein synthesis between immune cells or cardiac myocytes and no correlation between immune cell and cardiac myocyte areas for low-level protein synthesis. Our initial results may begin to show how injured hearts respond to areas of damage through protein synthesis and enable us to identify pathways to improve myocyte survival and preserve heart function in DMD patients.