Neutrophil extracellular traps and pyroptosis: a molecular nexus linking systemic autoimmune diseases to atherosclerosis.

摘要

This review aims to elucidate the molecular mechanisms of neutrophil extracellular traps (NETs) and pyroptosis, exploring their synergistic role as a pathological nexus bridging systemic autoimmune diseases with atherosclerosis. By systematically synthesizing recent literature and experimental evidence, we delineate the signaling cascades of these programmed inflammatory processes and analyze their contributions to disease progression in systemic lupus erythematosus, rheumatoid arthritis, and cardiovascular pathology. The analysis reveals a sophisticated bidirectional crosstalk, termed the NET-pyroptosis axis, which functions as a self-amplifying inflammatory loop that drives chronic tissue injury. Key findings highlight that while Gasdermin D serves as a context-dependent amplifier of NET release rather than a universal executioner, the Gasdermin E-mediated interaction between immune and stromal cells emerges as a critical driver of structural damage, such as synovial bone erosion and endothelial plaque denudation. Furthermore, we summarize emerging therapeutic strategies, including the pharmacological inhibition of peptidylarginine deiminase 4 and gasdermin pore formation, which hold significant promise for mitigating both systemic inflammation and the associated cardiovascular burden. Ultimately, this review establishes a novel pathophysiological framework that explains the heightened cardiovascular risk in autoimmune populations and provides a rationale for cross-disciplinary clinical interventions. Targeting the reciprocal interaction between these two inflammatory pathways may offer transformative breakthroughs in improving the long-term prognosis of patients with chronic inflammatory disorders.