Mechanisms that regulate macrophage burden in atherosclerosis

Area of Science:

• Cardiovascular Biology
• Immunology
• Atherosclerosis Research

Background:

• Mononuclear phagocytes (MPs), including monocytes, macrophages, and dendritic cells, are central to atherosclerosis.
• Historically, macrophage quantification in atherosclerotic lesions was limited.
• Technological progress is enhancing the study of dynamic MP populations within plaques.

Purpose of the Study:

• To review the evolution of atherosclerotic plaques focusing on changes in the MP compartment.
• To discuss the roles of MP recruitment, proliferation, and retention in plaque development, progression, and regression.
• To highlight current knowledge gaps and future research directions in MP biology and atherosclerosis.

Main Methods:

• Review of recent literature and innovative methods for interrogating MP biology in atherosclerotic plaques.
• Analysis of MP compartment dynamics from plaque initiation to regression.
• Identification of mechanisms regulating MP accumulation and function.

Main Results:

• Innovative methods have uncovered mechanisms governing MP accumulation and function in atherosclerotic plaques.
• The roles of MP recruitment, proliferation, and retention vary across different stages of plaque evolution.
• Key questions remain regarding cholesterol's role in macrophage accumulation and the interplay between innate and adaptive immunity in driving atherosclerosis.

Conclusions:

• Understanding MP dynamics is crucial for comprehending atherosclerosis.
• Future research should focus on distinguishing macrophage and dendritic cell roles and elucidating cholesterol-driven accumulation.
• Investigating the innate-adaptive immune crosstalk in atherosclerosis is essential for developing therapeutic strategies.