Macrophage profiling in atherosclerosis: understanding the unstable plaque

Area of Science:

• Cardiovascular Biology
• Immunology
• Atherosclerosis Research

Background:

• Atherosclerotic plaque development and rupture are primary causes of myocardial infarction and ischemic stroke.
• Monocyte and macrophage functions within the plaque microenvironment are critical drivers of disease progression.
• Macrophages exhibit diverse polarization states (e.g., M1, M2) and contribute to plaque stability or instability, with sex-specific differences observed.

Purpose of the Study:

• To review monocyte and macrophage phenotypes and functions in circulation and atherosclerotic lesions.
• To examine the contribution of these cells to stable versus unstable plaques in males and females.
• To highlight the impact of single-cell RNA sequencing on understanding immune cell signatures in atherosclerosis.

Main Methods:

• Review of existing literature on monocyte/macrophage biology in atherosclerosis.
• Analysis of findings from single-cell RNA sequencing studies.
• Discussion of high-dimensional approaches for immune cell profiling.

Main Results:

• Macrophages play a central role via oxidized LDL uptake and inflammatory responses, impacting plaque stability.
• Macrophage polarization is complex, extending beyond M1/M2 to include other populations.
• Single-cell approaches have redefined the understanding of immune cell clusters in the atherosclerotic niche.

Conclusions:

• Understanding diverse macrophage populations and their sex-specific roles is crucial for atherosclerosis.
• High-dimensional single-cell technologies are essential for dissecting complex immune signatures.
• Developing sex-specific immunotherapies holds promise for reducing cardiovascular event risk.