Systemic lupus erythematosus-accelerated atherosclerosis: mechanistic insights and clinical implications

Abstract

Premature coronary atherosclerosis remains a primary driver of late-stage mortality in systemic lupus erythematosus (SLE), independent of traditional cardiovascular risk profiles. This mini-review outlines the multifaceted immunometabolic pathways that underpin accelerated atherogenesis in SLE patients. We examine how chronic systemic inflammation modifies the lipoprotein profile toward a pro-oxidant state, characterized by dysfunctional HDL and elevated oxidized LDL. Central to this vascular pathology are type I interferon-driven cascades, excessive neutrophil extracellular trap release, and biased macrophage polarization toward pro-atherogenic phenotypes. Furthermore, the roles of pathogenic autoantibodies, genetic susceptibility, and the metabolic impact of specific immunosuppressants are explored. Integrating these mechanistic insights is essential for refining cardiovascular risk assessment and identifying novel immunomodulatory interventions. Ultimately, understanding the unique SLE-atherosclerosis axis provides a foundation for reducing cardiovascular morbidity and improving long-term outcomes in this vulnerable population.