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.