Duchenne muscular dystrophy (DMD) is a severe neuromuscular disease of skeletal and myocardial degeneration. Eventually, dilated cardiomyopathy develops from ischemia, inflammation and fibrosis. Due to the high mortality rate, there is an emerging need to diagnose DMD cardiomyopathy at early stages. Currently, DMD cardiomyopathy is diagnosed by imaging investigations and detection of circulating biomarkers. However, current imaging strategies detect functional and morphological changes but fall short in detecting molecular changes that underlie this disease. Circulating biomarkers provide information on the molecular level, but they are not cardiac-specific. Therefore, there is an emerging need for a biomarker that is endogenous to cardiac tissues. The growth hormone secretagogue receptor (GHSR) and its ligand, ghrelin are produced by both cardiomyocytes and vascular endothelial cells and could be an indicator of DMD cardiomyopathy. The work described in this thesis sought to characterize GHSR as a cardiac-localized biomarker in DMD cardiomyopathy. Histopathology and confocal imaging using a novel fluorescent ghrelin analog, Cy5-ghrelin(1-19), were used to investigate changes in cardiac tissue architecture and GHSR and inflammatory markers in the mdx:utrn-/- mouse model of DMD. My studies show that GHSR is elevated in mdx:utrn-/- myocardial tissues and correlate strongly with the macrophage marker F4-80 and the pro-inflammatory cytokine IL-6. Interestingly, I also show that both ghrelin and des-acyl ghrelin bind to sites in large cardiac vessels of mdx:utrn-/- which might be an indicator of vascular inflammation. Finally, my project shows the first report of GHSR in cardiac macrophages. In summary, my work suggests that, in dilated cardiomyopathy, elevations in GHSR correlate with the inflammatory phenotype as mediated by both the myocardium and macrophages
