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Isolation of Functional Cardiac Immune Cells
Published on: December 5, 2011
Mast cells in failing human hearts demonstrate transcriptomic activation of pathways involved in cardiac remodeling
Mikael Sandstedt1,2, Markus Johansson3, Marianne Jonsson1,2
1Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Insights
Intracardiac mast cells (CMCs) in failing human hearts show activated pathways linked to cardiac remodeling and inflammation. This study provides the first detailed characterization of CMCs in both healthy and failing human hearts.
Area of Science:
- Cardiology
- Immunology
- Molecular Biology
Background:
- Intracardiac mast cells (CMCs) are implicated in adverse cardiac remodeling and heart failure in animal models.
- The role of CMCs in human hearts has not been previously explored.
Purpose of the Study:
- To investigate the pathophysiological relevance of human CMCs in heart failure.
- To perform transcriptomic profiling of CMCs from failing and non-failing human hearts.
Main Methods:
- Biopsies from four heart chambers of heart failure patients (n=9) and organ donors (n=5) were analyzed.
- Flow cytometry identified C-kit+CD45+ CMCs and C-kit-CD45+ hematopoietic cells.
- Sorted cells underwent RNA sequencing for transcriptomic profiling.
Main Results:
- CMCs were identified in all analyzed hearts (failing and non-failing).
- CMCs from failing human hearts exhibited significantly activated pathways related to cardiac remodeling, fibrosis, and inflammation compared to non-failing hearts and other hematopoietic cells.
Conclusions:
- The study supports a role for mast cells in human heart failure.
- This research presents the first in-depth transcriptomic characterization of CMCs in non-failing and failing human hearts.
Abstract:
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.

