Pericardial Adipose Tissue Regulates Granulopoiesis, Fibrosis, and Cardiac Function After Myocardial Infarction

Area of Science:

• Immunology
• Cardiology
• Adipose Tissue Biology

Background:

• Pericardial adipose tissue (AT) harbors dense lymphoid clusters.
• The role of these lymphoid clusters in post-myocardial infarction (MI) inflammation and cardiac outcomes remains unclear.

Purpose of the Study:

• To investigate the role of pericardial AT lymphoid clusters in the inflammatory response following MI.
• To determine the impact of these clusters on cardiac function and fibrosis post-MI.

Main Methods:

• Examined pericardial AT lymphoid clusters in human and murine models of coronary artery disease and MI.
• Utilized B-cell depletion, granulocyte-macrophage colony-stimulating factor (GM-CSF) blockade, and CCR7-deficient mice to assess immune cell trafficking and function.
• Quantified leukocytes via flow cytometry and assessed cardiac fibrosis and ventricular function using histology and echocardiography.

Main Results:

• Larger B-cell clusters and increased GM-CSF-producing B cells were observed in pericardial AT of patients with coronary artery disease and in infarcted mice.
• Activated dendritic cells (DCs) migrated from infarcts to pericardial AT, promoting T-cell expansion.
• Pericardial AT manipulation (B-cell depletion, GM-CSF blockade, or AT removal) modulated immune cell responses, reduced cardiac neutrophil infiltration, and improved cardiac function in specific models.

Conclusions:

• Pericardial AT acts as a critical immune hub coordinating inflammatory responses after MI.
• This mechanism involves lymphoid clusters, B cells, and migrating DCs, influencing granulopoiesis and cardiac outcomes.
• Targeting pericardial AT immune functions may offer therapeutic strategies for post-MI recovery.