Good cop, bad cop? Rethinking the roles of cardiac macrophages in injury

Area of Science:

• Cardiovascular Biology
• Immunology
• Cell Biology

Background:

• Cardiac macrophages (CMs) are crucial for heart homeostasis and repair.
• Traditionally, embryonically derived CMs (em-CMs) were considered beneficial, while monocyte-derived CMs (mo-CMs) were deemed detrimental after cardiac injury.

Purpose of the Study:

• To challenge the binary classification of CMs based on their origin.
• To investigate the functional roles of expanded em-CMs and mo-CMs in cardiac injury models.

Main Methods:

• Utilized cardiac-specific genetic strategies to selectively expand either em-CM or mo-CM populations in mice.
• Assessed cardiac function following transverse aortic constriction (TAC)-induced injury.

Main Results:

• Expansion of mo-CMs led to adverse outcomes after TAC, as expected.
• Surprisingly, expansion of em-CMs also resulted in a marked decline in cardiac function post-TAC.
• The detrimental effect of expanded em-CMs was temporally dependent, occurring only when expanded before TAC induction, and involved interaction with mo-CMs.

Conclusions:

• The simplistic beneficial/detrimental classification of CMs based on origin is inadequate.
• Macrophage origin and timing of expansion significantly influence cardiac pathology and outcomes.
• Re-evaluation of CM function in heart injury is necessary, considering their complex interactions.