Mast cells in failing human hearts demonstrate transcriptomic activation of pathways involved in cardiac remodelling

<b>Aims:</b> Intracardiac mast cells (CMCs) have previously been shown to contribute to adverse remodelling and heart failure in animal models. As CMCs in human hearts remain unexplored, the aim of this study was to investigate the pathophysiological relevance of human CMCs through transcriptomic profiling. <b>Methods and Results:</b> Biopsies were collected from the four heart chambers of heart failure patients undergoing heart transplantation surgery (n = 9) as well as from deceased organ donors without chronic heart failure (n = 5). Using flow cytometry, C-kit+CD45+ CMCs and C-kit-CD45+ hematopoietic cells were identified in all failing and nonfailing hearts and were sorted for RNA sequencing analysis. In comparison to other hematopoietic C-kit-CD45+ cells and CMCs in nonfailing hearts, CMCs in failing hearts demonstrated significant activation of pathways involved in cardiac remodelling and heart failure, including fibrosis-associated and inflammatory pathways. <b>Conclusion:</b> Our results support a role for mast cells in human heart failure and constitute the first in-depth characterization of mast cells in the nonfailing and failing human heart.