Atherosclerosis in Rheumatoid Arthritis: The Role of NETs and Management

Rheumatoid arthritis (RA), a chronic inflammatory autoimmune disease, is associated with an increased the risk of cardiovascular disease (CVD), with atherosclerosis as the primary pathological basis. Neutrophil extracellular traps (NETs) represent a plausible pathogenic contributor and biomarker candidate linking RA to accelerated atherosclerosis. This review summarizes the key regulatory factors for the formation of NETs in RA, including autoantibodies, proinflammatory cytokines, cellular crosstalk, post-translational modifications, impaired clearance and neutrophil heterogeneity. Notably, most available supporting evidence is derived from mechanistic studies, preclinical models and associative clinical observations, rather than definitive causal interventional trials. Accumulating evidence suggests that NETs may contribute to RA-associated atherosclerosis via three proposed pathways: endothelial dysfunction, inflammatory plaque progression and instability, and thrombosis. Additionally, this review outlines the multimodal management strategies, encompassing NETs-targeted interventions, RA inflammation control, traditional CVD risk management and biomarker-guided risk stratification. NETs hold promise as a potential therapeutic target to mitigate CVD morbidity and mortality in patients with RA, though further translational and clinical validation is needed.