The Dual Role of Macrophages in MIRI and MI by Immunity and Inflammation: Damage, Repair, Crosstalk, and Therapy

Area of Science:

• Cardiovascular Biology
• Immunology
• Regenerative Medicine

Background:

• Coronary artery disease (CAD) prevalence is rising globally, leading to myocardial infarction (MI) and ischemia/reperfusion injury (MIRI).
• Macrophages are crucial for resolving inflammation and promoting repair after cardiac injury, but their roles differ in MI and MIRI.
• Understanding macrophage subsets is vital for developing effective cardiac treatments.

Purpose of the Study:

• To elucidate the distinct roles of C─C chemokine receptor type 2 (CCR2)^high and triggering receptor expressed on myeloid cells 2 (TREM2)^high macrophages in myocardial infarction (MI) and ischemia/reperfusion injury (MIRI).
• To examine the crosstalk between macrophages, neutrophils, and other immune cells in cardiac injury.
• To discuss potential macrophage-targeted therapies for mitigating cardiac damage.

Main Methods:

• Review and analysis of existing literature on macrophage subsets in cardiac injury models.
• Comparative examination of pathogenic mechanisms in MI versus MIRI.
• Exploration of immune cell interactions and therapeutic strategies.

Main Results:

• CCR2^high macrophages dominate early MI phases, while TREM2^high macrophages are prevalent in later stages.
• Distinct macrophage subsets orchestrate inflammation resolution and repair-remodeling processes differently in MI and MIRI.
• Macrophage crosstalk with neutrophils and other immune cells significantly influences cardiac injury outcomes.

Conclusions:

• Targeting specific macrophage subsets (CCR2^high and TREM2^high) holds therapeutic potential for both MI and MIRI.
• Macrophage-centered therapies, including anti-inflammatory modulation, exosome delivery, and stem cell interventions, can mitigate cardiac injury progression.
• Further research into macrophage heterogeneity and function is essential for advancing cardiovascular disease treatment.