MacroERA: non-coding RNA modulate macrophage function during heart failure. (MacroERA)

Current heart failure therapy primarily addresses cardiac myocytes and vascular smooth muscle cells. The narrow focus on these two cell types neglects accumulating evidence that also other cardiac cell types – endothelial cells, fibroblasts and immune cells – impact on cardiac homeostasis, disease development and manifestation. Although macrophages are the largest fraction of immune cells in native mammalian myocardium, their roles in this organ are insufficiently resolved. This applies particularly to the resident type of macrophages, which is from a different (developmental) origin than monocyte-derived macrophages. The function of these resident cardiac macrophages is entirely unclear. Non-coding RNA, such as microRNAs (miRNAs), are likely to exert critical activities in cardiac macrophages, given preliminary data from our consortium that identify miRNAs in these cells as modulators of their polarization, but also of myocyte hypertrophy. Moreover, we find miRNAs in exosomes secreted by cardiac cells as an intercellular signal for macrophages. The labs involved in this joint project pursue the idea that cardiac disease progression is determined by ncRNAs that regulate macrophage function. To exploit the potential of macrophage ncRNAs for heart failure therapy, we aim to identify, characterize and manipulate macrophage miRNAs, both in myocardium and in blood, from human patients and mouse disease models.