To summarize recent advances in understanding macrophage heterogeneity in human atherosclerosis through single-cell and spatial profiling, and to establish a coherent framework for clinical application, including risk stratification and therapeutic targeting.
Key Findings:
Macrophages in atherosclerotic plaques exhibit diverse states: inflammatory, interferon-responsive, lipid-associated, foamy, resident-like, and reparative, each linked to specific clinical outcomes.
These macrophage states are associated with clinically relevant features such as symptomatic disease, necrotic core expansion, and plaque instability.
Methodological heterogeneity in plaque studies complicates cross-study comparisons and biological concordance, impacting the reliability of findings.
Interpretation:
The study highlights the importance of macrophage diversity in atherosclerosis and its implications for disease progression and clinical outcomes, suggesting targeted therapies could be developed based on macrophage state.
Limitations:
Variability in plaque procurement and anatomical annotation can distort macrophage state recovery, potentially leading to misinterpretation of data.
Lack of standardized nomenclature and computational integration strategies hinders comparisons across studies, complicating the establishment of a unified understanding.
Conclusion:
A coherent human plaque macrophage atlas is essential for translating macrophage state signatures into clinical applications for risk stratification and therapeutic targeting, ultimately improving patient outcomes.
Population-based cohort shows higher rates of cardiac arrhythmias and coronary artery disease following nonhospitalized infections, with sex-specific differences.
