Resident and recruited macrophages differentially contribute to cardiac healing after myocardial ischemia

Area of Science:

• Immunology
• Cardiovascular Biology
• Cellular Biology

Background:

• Cardiac macrophages are diverse, with functions linked to their origin.
• The specific roles of different macrophage subsets in ischemia/reperfusion (I/R) injury are not fully understood.

Purpose of the Study:

• To investigate the distinct roles of resident and recruited cardiac macrophages in I/R injury.
• To determine how targeting colony-stimulating factor 1 receptor (CSF1R) affects macrophage populations and cardiac outcomes.

Main Methods:

• Utilized genetic deletion of a regulatory element in the Csf1r locus to specifically eliminate resident macrophages.
• Employed continuous CSF1R inhibition to deplete both resident and recruited macrophages.
• Assessed immune cell crosstalk, neutrophil polarization, cardiac remodeling, infarct size, and cardiac function post-I/R injury.

Main Results:

• Specific absence of resident macrophages impaired cardiac remodeling by altering immune crosstalk and promoting proinflammatory neutrophil polarization, without affecting infarct size.
• Continuous CSF1R inhibition depleted all macrophages, leading to adverse cardiac remodeling, increased infarct size, and worsened cardiac function.
• Resident macrophages were found to orchestrate inflammation for improved cardiac remodeling, while recruited macrophages influenced infarct size.

Conclusions:

• Resident macrophages play a crucial role in improving cardiac remodeling post-myocardial infarction.
• Recruited macrophages are critical determinants of infarct size and overall cardiac function after I/R injury.
• Distinct macrophage populations have specific beneficial effects in myocardial infarction contexts.