Bleomycin induces endothelial cell pyroptosis and regulates fibrosis by activating the NLRP3/caspase-1/GSDMD pathway: a possible mechanism contributing to the sclerotherapy of venous malformations

Abstract

Venous malformations (VMs) are slow-flow vascular anomalies that pose significant health challenges. Bleomycin (BLM) is frequently used in Sclerotherapy for VMs, but its mechanism, particularly through pyroptosis, remains poorly understood. This study explores the role of BLM-induced endothelial cell pyroptosis in VMs sclerotherapy and its regulatory effects on fibrosis via the NLRP3/caspase-1/GSDMD pathway. Using a combination of TUNEL staining, Western blotting, and immunohistochemistry, we investigated the effects of BLM on VMs and endothelial cells in vitro. Pyroptosis and fibrosis were quantified, and the involvement of the NLRP3/caspase-1/GSDMD pathway was assessed. BLM treatment significantly increased pyroptosis and fibrosis in VMs tissues and cultured endothelial cells. Activation of the NLRP3/caspase-1/GSDMD pathway was crucial for these effects, which could be mitigated by pathway inhibition. BLM regulates fibrosis and induces pyroptosis through the NLRP3/caspase-1/GSDMD pathway in VMs. Understanding this mechanism could enhance the effectiveness and safety of Sclerotherapy in clinical settings.