Professor Jiangsu University Zhenjiang, Jiangsu, China (People's Republic)
Introduction/Rationale: Myocardial Infarction (MI), a common cardiovascular disease, leads to myocardial ischemia, hypoxia, and dysfunction, with different inflammatory cells involved in the pathogenesis. Recently, we noticed a significant increase in cardiac mast cells following injury. The roles and locations of increased mast cells in a damaged heart are unclear.
Methods: Flow cytometry, KitW-sh/W-sh and Cma1-Cre; iDTR transgenic mice, transplantation, and spatial transcriptomics are employed to address the above question.
Results: Our result demonstrated that the number of mast cells in the mouse heart increased. Inhibiting the activation of mast cells or using KitW-sh/W-sh and Cma1-Cre; iDTR mice significantly ameliorated the inflammation and collagen deposition, specific to the fibrosis. The bioinformatic analysis showed a potential connection between macrophages and cardiac mast cells following MI. We confirm the detailed mechanism by which the infiltrated macrophage activates the mast cell, releasing intracellular particles that lead to cardiac fibrosis. Furthermore, we demonstrated that the cardiac mast cell is derived from the mast cell progenitors of pericardial adipose tissue (PAT). The transplantation or excision of the PAT model confirmed this phenomenon. We also observed a similar mechanism in human spatial transcriptomics.
Conclusion: Our results identified the novel roles of mast cells derived from PAT, which may shed light on cardiac therapy following injury.
