TREM2 protects from atherosclerosis by limiting necrotic core formation.

Area of Science:

• Cardiovascular Biology
• Immunology
• Cell Biology

Background:

• Atherosclerosis is a leading cause of global mortality, characterized by lipid accumulation and inflammation in artery walls.
• Triggering receptor expressed on myeloid cells 2 (TREM2), a lipid-sensing receptor, is found in macrophage foam cells in atherosclerosis.
• The precise function of TREM2 in the development of atherosclerosis remains incompletely understood.

Purpose of the Study:

• To investigate the role of TREM2 in the pathogenesis of atherosclerosis.
• To determine how TREM2 influences macrophage behavior and plaque development in early atherosclerosis.

Main Methods:

• Utilized hematopoietic or global TREM2-deficient mouse models.
• Administered TREM2 agonists to assess their impact on atherosclerotic plaques.
• Examined necrotic core formation and macrophage efferocytosis and survival in atherosclerotic lesions.

Main Results:

• Hematopoietic or global TREM2 deficiency led to increased necrotic core formation in early atherosclerosis.
• TREM2 agonism resulted in decreased necrotic core formation.
• TREM2 was found to be essential for macrophage efferocytosis and the survival of lipid-laden macrophages.

Conclusions:

• TREM2 plays a critical role in regulating the balance between foam cell death and clearance within atherosclerotic lesions.
• TREM2 modulates plaque necrosis, suggesting it as a potential therapeutic target for atherosclerosis.