Ricerc@Sapienza

Cardio-respiratory failure is the major cause of death in patients of Duchenne Muscular Dystrophy (DMD), mainly due to diaphragm and heart fibrosis. It is well recognized that immune cells play a crucial role in regulating cardiac function, as well as fibrotic deposition, and there is growing appreciation of immune system involvement in ischaemic heart disease, as well as in non- ischaemic myocarditis. However, very little is known about the involvement of immune system in the cardiac functional defects observed in DMD. We recently found a previously undescribed macrophage subpopulation present in the heart and diaphragm from both WT and mdx (the mouse model of DMD) mice, based on a very high level of expression of F4/80 (F4/80hi) , which is not present in the limb muscle, and distinct from the classical F4/80 expressing population. In this context, it has been clearly demonstrated that cardiac macrophages are numerous, heterogenous and ontogenically diverse, and that different subpopulations might be involved in different cardiac functions. We aim to analyse in detail the relative abundance and kinetics of this population during the progression of the disease in mdx, compared to WT, by cytofluorimetric analysis. We will then analyse the trascriptome of this population FACS-sorted from the heart and diaphragm of both WT and mdx mice at different ages, and compare with that obtained from the classical F4/80 expressing population FACS-sorted from the same organs. The accomplishment of this study might add new insight on the role of different immune cell populations in the pathophysiological events regulating the cardio-respiratory defects observed in DMD patients.