Högskolan i Skövde

Intracardiac mast cells (CMCs) have previously been shown to contribute to adverse remodeling 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. 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 with other hematopoietic C-kit-CD45+ cells and CMCs in nonfailing hearts, CMCs in failing hearts demonstrated significant activation of pathways involved in cardiac remodeling and heart failure, including fibrosis-associated and inflammatory pathways. 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.

NEW & NOTEWORTHY Intracardiac mast cells (CMCs) have been shown to contribute to remodeling and fibrosis in animal models. No phenotypical characterization of human CMCs has been conducted before the current transcriptomic profiling study. CMCs isolated from failing human hearts demonstrated activated pathways involved in cardiac remodeling and fibrosis, both compared with other hematopoietic cells and to CMCs in nonfailing hearts. The study suggests that CMCs may constitute a novel candidate for modulation in human heart failure.