Heterogeneity of atherosclerotic plaque macrophage origin, phenotype and functions: Implications for treatment

Area of Science:

• Immunology
• Cardiovascular Biology
• Cell Biology

Background:

• Macrophages are central to atherosclerotic lesions, influencing inflammation and plaque stability.
• Monocytes were traditionally viewed as the primary source of macrophages in plaques.
• Emerging evidence suggests local macrophage proliferation and transdifferentiation from vascular cells are alternative sources.

Purpose of the Study:

• To review advances in understanding monocyte and macrophage heterogeneity.
• To explore the implications of this heterogeneity for therapeutic interventions.
• To identify strategies for reducing cardiovascular event risk without compromising immune response.

Main Methods:

• Literature review of recent research on macrophage biology in atherosclerosis.
• Analysis of studies on monocyte differentiation and macrophage phenotypes.
• Synthesis of findings on therapeutic targeting of macrophage subsets.

Main Results:

• Macrophages exhibit significant heterogeneity in phenotype and function within atherosclerotic plaques.
• Multiple sources contribute to plaque macrophage populations, including monocytes, local proliferation, and transdifferentiation.
• Specific macrophage subsets play distinct roles in disease progression and plaque stability.

Conclusions:

• Targeting specific monocyte and macrophage subsets offers a promising therapeutic avenue for atherosclerosis.
• A deeper understanding of macrophage heterogeneity is essential for developing effective and safe cardiovascular treatments.
• Personalized therapeutic strategies may be developed based on distinct macrophage roles in individual patients.