Objective:

To synthesize current evidence on the immune-metabolic-vascular interplay in systemic lupus erythematosus (SLE) and its critical role in accelerated atherosclerosis.

Approach:

Key Findings:

• SLE patients have a significantly higher risk of premature atherosclerosis and ASCVD not fully explained by traditional risk factors, necessitating further investigation.
• Type I interferon (IFN-I) is associated with endothelial injury and impaired vascular repair, indicating a target for therapeutic intervention.
• Neutrophil extracellular traps (NETs) and oxidative modification contribute to dysfunctional high-density lipoprotein (HDL), suggesting a pathway for treatment.
• Monocyte/macrophage reprogramming promotes foam-cell formation and inflammation, highlighting the role of immune cells in atherosclerosis.
• T- and B-cell metabolic dysregulation sustains vascular inflammation and autoantibody-driven injury, pointing to the need for immune-targeted therapies.

Interpretation:

The interplay between immune activation and metabolic dysregulation in SLE is crucial for understanding accelerated atherosclerosis, with significant implications for treatment strategies.

Limitations:

• Most evidence is based on mechanistic studies and biomarker readouts rather than dedicated clinical trials, underscoring the need for more robust research.
• Current studies often focus on surrogate endpoints rather than direct cardiovascular outcomes, indicating a gap in the literature that needs addressing.

Conclusion:

Future strategies for treating SLE-related atherosclerosis should integrate metabolic and immune-targeted approaches, emphasizing the urgency of this integration in clinical practice.

Attribution Notice

This content is an AI-generated, fully rewritten summary based on a published scholarly article. It does not reproduce the original text and is not a substitute for the original publication. Readers are encouraged to consult the source for full context, data, and methodology.