Innate Immunity Effector Cells as Inflammatory Drivers of Cardiac Fibrosis

Area of Science:

• Cardiovascular Biology
• Immunology
• Pathology

Background:

• Cardiovascular diseases (CVDs) remain a leading global cause of death, with cardiac fibrosis and extracellular matrix (ECM) remodeling being critical factors in disease progression.
• While fibrosis is a common feature of CVDs, the precise mechanisms driving it and effective clinical interventions are still lacking.
• Immune cells play a significant role in sterile inflammation following cardiac injury, initiating fibrotic responses.

Purpose of the Study:

• To review and discuss the contribution of innate immune cells to cardiac fibrosis.
• To elucidate the mechanisms by which immune cells modulate the myocardial microenvironment and orchestrate fibrogenesis.
• To highlight the potential for targeting immune cell activity in developing novel antifibrotic therapies for CVDs.

Main Methods:

• Review of existing literature on immune cell involvement in cardiac fibrosis.
• Discussion of the roles of neutrophils, macrophages, natural killer cells, eosinophils, and mast cells in the fibrotic process.
• Analysis of the interplay between immune cells, fibroblasts, and other cardiac cells.

Main Results:

• Innate immune cells infiltrate injured hearts and release pro-inflammatory cytokines that activate myofibroblasts, driving fibrosis.
• The complex interactions between various immune and non-immune cells are central to the development of cardiac fibrosis.
• Specific immune cell types orchestrate the fibrogenic process within the injured myocardial microenvironment.

Conclusions:

• Immune cell-mediated inflammation is a major driver of cardiac fibrosis and ECM remodeling.
• A detailed understanding of immune cell infiltration dynamics and functions in the injured heart is crucial.
• Targeting innate immune responses presents a promising therapeutic strategy for mitigating cardiac fibrosis and improving CVD outcomes.