THE CARDIOSPLENIC AXIS IS ESSENTIAL FOR THE PATHOGENESIS OF ISCHEMIC HEART FAILURE

Area of Science:

• Immunology
• Cardiology
• Pathology

Background:

• The role of the immune system in heart failure (HF) pathogenesis remains unclear.
• Innate and adaptive immune responses are critical in many diseases, but their specific involvement in HF is not well-defined.

Purpose of the Study:

• To investigate the involvement of innate and adaptive immunity in the development of ischemic heart failure (HF).
• To elucidate the role of the spleen and splenic immune cells in HF progression and cardiac remodeling.

Main Methods:

• Analysis of immune cell populations (monocytes, macrophages, dendritic cells, T cells) in mice with ischemic HF.
• Assessment of splenic remodeling and antigen processing.
• Experimental manipulations including splenectomy, adoptive transfer of splenocytes and T cells, and T cell depletion.

Main Results:

• Ischemic HF mice showed significant expansion of proinflammatory monocytes/macrophages, dendritic cells, and CD4+/CD8+ T cells.
• The spleen exhibited remodeling with heightened antigen processing and expanded antigen-experienced effector/memory CD4+ T cells.
• Activated splenic immune cells were found to drive chronic inflammation, traffic to the heart, and promote pathological cardiac remodeling.

Conclusions:

• The spleen is central to the immune response in HF, with activated splenic immune cells contributing to chronic inflammation and cardiac remodeling.
• Ischemic cardiomyopathy may be an immune-mediated disease targeting cardiac antigens, with the spleen playing a critical role.
• Immune memory within splenic cells contributes to tissue injury and pathological cardiac remodeling in HF.