Ginkgolide C alleviates atherosclerosis by activating LAMP-2A to enhance chaperone-mediated autophagy and promote NLRP3 inflammasome degradation.

Introduction: The NLRP3 inflammasome/IL-1β-dependent inflammatory response serves as a critical factor and key trigger in exacerbating atherosclerosis (AS), whereas chaperone-mediated autophagy (CMA) recognizes and degrades the NLRP3 inflammasome. Targeting this pathway represents a more nuanced and targeted anti-inflammatory strategy to mitigate AS progression. As a key bioactive component derived from Method: This study established both Result: Our results demonstrate that GC potentiated CMA activity in macrophages, leading to promoted degradation of the NLRP3 inflammasome via the lysosomal pathway. This process effectively suppressed the NLRP3 inflammasome/IL-1β-driven inflammatory cascade, ultimately attenuating atherosclerotic progression. Conclusion: GC alleviates AS via a novel LAMP-2A-dependent mechanism that enhances protein clearance and suppresses NLRP3 inflammation, providing a targeted alternative to broad immunosuppression. These results establish GC as a promising therapeutic candidate and prompt further studies on its clinical efficacy and applicability in other chronic inflammatory diseases.