The Impact of PCSK9 Inhibitors on Circulatory Inflammation: Mechanisms, Evidence, and Application Prospects

To systematically review and analyze the impact of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on circulating inflammation, focusing on their underlying mechanisms and clinical application prospects, this review comprehensively summarizes recent studies addressing the molecular basis, nonclassical pathologic mechanisms, clinical evidence in multisystem diseases, therapeutic advances, and combined intervention strategies associated with PCSK9 and its inhibitors, highlighting their anti-inflammatory potential and personalized management strategies. PCSK9 participates in circulating inflammation primarily through multiple signaling pathways, including the NOD-like receptor family pyrin domain containing 3 inflammasome and the Toll-like receptor 4/nuclear factor kappa B axis. Clinical evidence indicates that PCSK9 inhibitors have limited direct effects on traditional inflammatory biomarkers. However, they show benefits in improving atherosclerotic plaque stability and modulating immune-inflammatory gene expression. The anti-inflammatory effects of PCSK9 inhibitors in circulating inflammation might not be directly reflected through changes in conventional inflammatory biomarkers. Future research should further explore their nonclassical mechanisms and optimize personalized risk stratification strategies, integrating multiomics and multiple biomarkers for precise inflammation management.